Spatial and temporal information processing in the sea urchin embryo: modular and intramodular organization of the CyIIIa gene cis-regulatory system

The CyIIIa cytoskeletal actin gene of Strongylocentrotus purpuratus is expressed specifically in the aboral ectoderm. In earlier work we identified a 2.3 kb cis-regulatory region that is necessary and sufficient for correct spatial and temporal expression of a CyIIIa.CAT gene. This region includes about 20 sites of specific protein-DNA interaction, at which at least nine different transcription factors may be bound. All except two of these factors have been cloned. In this work we have analyzed by deletion or mutagenesis each specific interaction. A specific function was identified for every binding site examined. These individual functions include control of amplitude and timing of expression at different phases of embryogenesis, and control of spatial expression. We show that particular negative regulatory interactions are required to repress expression of the CyIIIa.CAT construct in oral ectoderm and in skeletogenic mesenchyme at different stages. In further experiments we determined the overall functional organization of the CyIIIa cis-regulatory system, and we show that this system is modular in its regulatory structure. The ‘proximal module’ (with respect to the transcription start site) extends upstream for about 800 base pairs, and includes nine target sites serviced by six different transcription factors. Its major role is to establish CyIIIa expression in the aboral ectoderm territory as the blastomere founder cells are specified and the oral-aboral axis is determined, and to activate the CyIIIa gene late in cleavage. The ‘middle module,’ which lies upstream of the proximal module, acquires major control of CyIIIa function after the blastula stage. It includes six target sites, serviced by four different factors. The middle module is responsible for a sharp increase in expression occurring during gastrulation, mediated by the positively acting factors that bind within it. The middle module also includes sites at which two different negatively acting spatial control factors bind, the functions of which are required for correct spatial expression late in embryogenesis. The ‘distal module’ contains a number of sites at which a positively acting factor binds, but this module exercises no spatial regulatory function. Interactions within the distal module are required for the normal levels of function of both the proximal and middle modules

An investigation of the optimal conditions of rocket motion in the vicinity of a planet

Optimal control of points of motion for mass transfer in vacuums in gravitational fiel

Constraints on scalar diffusion anomaly in three-dimensional flows having bounded velocity gradients

This study is concerned with the decay behaviour of a passive scalar $\theta$ in three-dimensional flows having bounded velocity gradients. Given an initially smooth scalar distribution, the decay rate $d/dt$ of the scalar variance $$ is found to be bounded in terms of controlled physical parameters. Furthermore, in the zero diffusivity limit, $\kappa\to0$, this rate vanishes as $\kappa^{\alpha_0}$ if there exists an $\alpha_0\in(0,1]$ independent of $\kappa$ such that $<\infty$ for $\alpha\le\alpha_0$. This condition is satisfied if in the limit $\kappa\to0$, the variance spectrum $\Theta(k)$ remains steeper than $k^{-1}$ for large wave numbers $k$. When no such positive $\alpha_0$ exists, the scalar field may be said to become virtually singular. A plausible scenario consistent with Batchelor's theory is that $\Theta(k)$ becomes increasingly shallower for smaller $\kappa$, approaching the Batchelor scaling $k^{-1}$ in the limit $\kappa\to0$. For this classical case, the decay rate also vanishes, albeit more slowly -- like $(\ln P_r)^{-1}$, where $P_r$ is the Prandtl or Schmidt number. Hence, diffusion anomaly is ruled out for a broad range of scalar distribution, including power-law spectra no shallower than $k^{-1}$. The implication is that in order to have a $\kappa$-independent and non-vanishing decay rate, the variance at small scales must necessarily be greater than that allowed by the Batchelor spectrum. These results are discussed in the light of existing literature on the asymptotic exponential decay $\sim e^{-\gamma t}$, where $\gamma>0$ is independent of $\kappa$.Comment: 6-7 journal pages, no figures. accepted for publication by Phys. Fluid

Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49oC) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid- cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum

Genomic homogeneity in fibrolamellar carcinomas

Background-Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AF-FCR) technique to detect genetic alterations in this disease.Aim-The aim of this study was to assess the degree of genomic heterogeneity of FEC using the AP-PCR technique. Methods-A fetal of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers.Results-DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed.Conclusions-Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC

Wave Function of a Brane-like Universe

Within the mini-superspace model, brane-like cosmology means performing the variation with respect to the embedding (Minkowski) time $\tau$ before fixing the cosmic (Einstein) time $t$. The departure from Einstein limit is parameterized by the 'energy' conjugate to $\tau$, and characterized by a classically disconnected Embryonic epoch. In contrast with canonical quantum gravity, the wave-function of the brane-like Universe is (i) $\tau$-dependent, and (ii) vanishes at the Big Bang. Hartle-Hawking and Linde proposals dictate discrete 'energy' levels, whereas Vilenkin proposal resembles $\alpha$-particle disintegration.Comment: Revtex, 4 twocolumn pages, 3 eps figures (accepted for publication in Class. Quan. Grav.

The eta-photon transition form factor

The eta-photon transition form factor is evaluated in a formalism based on a phenomenological description at low values of the photon virtuality, and a QCD-based description at high photon virtualities, matching at a scale $Q_{0}^{2}$. The high photon virtuality description makes use of a Distribution Amplitude calculated in the Nambu-Jona-Lasinio model with Pauli-Villars regularization at the matching scale $Q_{0}^{2}$, and QCD evolution from $Q_{0}^{2}$ to higher values of $Q^{2}$. A good description of the available data is obtained. The analysis indicates that the recent data from the BaBar collaboration on pion and eta transition form factor can be well reproduced, if a small contribution of twist three at the matching scale $Q_{0}^{2}$ is included.Comment: 14 pages, 3 figures, revised version, minor corrections, references added, conclusions unchanged. Accepted for publication in Phys. Rev.

Evidence for prelocalization of cytoplasmic factors affecting gene activation in early embryogenesis

Differentiation begins early in embryogenesis as different genes become active in different cells. Within the closed system of the early embryo, equal genomes thus direct the creation of diverse cell types. Though the nuclei of these cells contain complete copies of the same genome,(1,2) the nucleoplasmic and cytoplasmic environments of these genomes are not the same, as a result of the distribution of cleavage nuclei into diverse areas of egg cytoplasm early in the cleavage process. In some cases the fate of these nuclei, i.e., the type of differentiated cell to which they or their descendants give rise, has been seen to depend on the area of cytoplasm in which they come to lie

Multistable alignment states in nematic liquid crystal filled wells

Two distinct, stable alignment states have been observed for a nematic liquid crystal confined in a layer with thickness of 12 μm and in square wells with sides of length between 20 and 80 μm. The director lies in the plane of the layer and line defects occur in two corners of the squares. The positions of the defects determine whether the director orientation is across the diagonal or is parallel to two opposite edges of the square. The device is multistable because both the diagonal and parallel states are stable when rotated by multiples of 90° in plane