Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis

Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR) binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression

Model reduction in the back step fluid–thermal problem with variable geometry

A methodology is presented to undertake the development of reduced-order models (ROMs) in variable geometry fluid–thermal problems using the method of snapshots. First, some snapshots are calculated in computational domains that vary in both shape and number of grid points. These snapshots are projected onto a so-called virtual grid (defined in a virtual geometry) using a smooth transformation. Proper orthogonal decomposition (POD) modes are obtained from the associated virtual snapshots and projected back onto the original grids, where they are used to define expansions of the flow variables. The associated POD mode amplitudes are obtained minimizing a residual, which is calculated in terms of the reconstructed solution. POD modes are calculated using only a part of the computational domain, which will be called the projection window, and the residual is defined using only a limited number of points of the computational domain. This methodology is illustrated addressing the problem of heat transfer downstream of a backward facing step in the 2-D steady, laminar regime, with three free parameters, namely the Reynolds number, the wall temperature, and the step height

PLANEACIÓN DIDÁCTICA GENERAL DE LA ASIGNATURA: ECONOMÍA

GUÍA DIDÁCTICA / PLANEACIÓN DIDÁCTICA (NMS

Stellar Disks in Aquarius Dark Matter Haloes

We investigate the gravitational interactions between live stellar disks and their dark matter halos, using LCDM haloes similar in mass to that of the Milky Way taken from the Aquarius Project. We introduce the stellar disks by first allowing the haloes to respond to the influence of a growing rigid disk potential from z = 1.3 to z = 1.0. The rigid potential is then replaced with star particles which evolve self-consistently with the dark matter particles until z = 0.0. Regardless of the initial orientation of the disk, the inner parts of the haloes contract and change from prolate to oblate as the disk grows to its full size. When the disk normal is initially aligned with the major axis of the halo at z=1.3, the length of the major axis contracts and becomes the minor axis by z=1.0. Six out of the eight disks in our main set of simulations form bars, and five of the six bars experience a buckling instability that results in a sudden jump in the vertical stellar velocity dispersion and an accompanying drop in the m=2 Fourier amplitude of the disk surface density. The bars are not destroyed by the buckling but continue to grow until the present day. Bars are largely absent when the disk mass is reduced by a factor of two or more; the relative disk-to-halo mass is therefore a primary factor in bar formation and evolution. A subset of the disks is warped at the outskirts and contains prominent non-coplanar material with a ring-like structure. Many disks reorient by large angles between z=1 and z=0, following a coherent reorientation of their inner haloes. Larger reorientations produce more strongly warped disks, suggesting a tight link between the two phenomena. The origins of bars and warps appear independent: some disks with strong bars show no disturbances at the outskirts, while the disks with the weakest bars show severe warps.Comment: 19 pages, 13 figures, accepted MNRAS; fixed compatibility problem in figures 8,

Counterion Condensation and Fluctuation-Induced Attraction

We consider an overall neutral system consisting of two similarly charged plates and their oppositely charged counterions and analyze the electrostatic interaction between the two surfaces beyond the mean-field Poisson-Boltzmann approximation. Our physical picture is based on the fluctuation-driven counterion condensation model, in which a fraction of the counterions is allowed to ``condense'' onto the charged plates. In addition, an expression for the pressure is derived, which includes fluctuation contributions of the whole system. We find that for sufficiently high surface charges, the distance at which the attraction, arising from charge fluctuations, starts to dominate can be large compared to the Gouy-Chapmann length. We also demonstrate that depending on the valency, the system may exhibit a novel first-order binding transition at short distances.Comment: 15 pages, 8 figures, to appear in PR

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

A new framework to enable equitable outcomes: resilience and nexus approaches combined

Managing integrated social-ecological systems to reduce risks to human and environmental well-being remains challenging in light of the rate and extent of undesirable changes that are occurring. Developing frameworks that are sufficiently integrative to guide research to deliver the necessary insights into all key system aspects is an important outstanding task. Among existing approaches, resilience and nexus framings both allow focus on unpacking relationships across scales and levels in a system and emphasize the involvement of different groups in decision making to different extents. They also suffer weaknesses and neither approach puts social justice considerations explicitly at its core. This has important implications for understanding who wins and loses out from different decisions and how social and ecological risks and trade-offs are shared and distributed, temporally and spatially. This paper conceptually integrates resilience and nexus approaches, developing a combined framework and indicating how it could effectively be operationalized in cases from mountain and mangrove social-ecological systems. In doing so, it advances understanding of complex social-ecological systems framings for risk-based decision making beyond that which could be achieved through use of either resilience or nexus approaches alone. Important next steps in testing the framework involve empirical and field operationalization, requiring interdisciplinary, mixed method approache