Evolutionary plasticity of developmental gene regulatory network architecture

Sea stars and sea urchins evolved from a last common ancestor that lived at the end of the Cambrian, approximately half a billion years ago. In a previous comparative study of the gene regulatory networks (GRNs) that embody the genomic program for embryogenesis in these animals, we discovered an almost perfectly conserved five-gene network subcircuit required for endoderm specification. We show here that the GRN structure upstream and downstream of the conserved network kernel has, by contrast, diverged extensively. Mesoderm specification is accomplished quite differently; the Delta–Notch signaling system is used in radically distinct ways; and various regulatory genes have been coopted to different functions. The conservation of the conserved kernel is thus the more remarkable. The results indicate types of network linkage subject to evolutionary change. An emergent theme is that subcircuit design may be preserved even while the identity of genes performing given roles changes because of alteration in their cis-regulatory control systems

Increased duration of co-contraction of medial knee muscles is associated with greater progression of knee osteoarthritis

Background: As knee osteoarthritis (OA) cannot be cured, treatments that slow structural disease progression are a priority. Knee muscle activation has a potential role in OA pathogenesis. Although enhanced knee muscle co-contraction augments joint stability; this may speed structural disease progression by increased joint load. Objective: This study investigated the relationship between cartilage loss and duration of co-contraction of medial/lateral knee muscles in medial knee OA. Design: Prospective cohort study. Methods: Medial (vastus medialis; semimembranosus) and lateral (vastus lateralis; biceps femoris) knee muscle myoelectric activity was recorded in 50 people with medial knee OA during natural speed walking at baseline. Medial tibial cartilage volume was measured from MRI at baseline and 12 months. Relationships between percent volume loss and duration of co-contraction of medial/lateral muscles around stance phase and ratio of duration of medial to lateral muscle co-contraction were evaluated with multiple linear regression. Results: Greater duration of medial muscle co-contraction and greater duration of medial relative to lateral co-contraction correlated positively with annual percent loss of medial tibial cartilage volume (. P = 0.003). Estimated cartilage loss was 0.14 (95% confidence interval -0.23 to -0.05) greater for each increase in medial muscle co-contraction duration of 1% of the gait cycle. Lateral muscle co-contraction inversely correlated with cartilage loss. Conclusion: Data support the hypothesis that augmented medial knee muscle co-contraction underpins faster progression of medial knee OA. Increased duration of lateral muscle co-contraction protected against medial cartilage loss. Exercise and biomechanical interventions to change knee muscle activation patterns provide possible candidates to slow progression of knee OA

RNA deep sequencing reveals differential MicroRNA expression during development of sea urchin and sea star

microRNAs (miRNAs) are small (20-23 nt), non-coding single stranded RNA molecules that act as post-transcriptional regulators of mRNA gene expression. They have been implicated in regulation of developmental processes in diverse organisms. The echinoderms, Strongylocentrotus purpuratus (sea urchin) and Patiria miniata (sea star) are excellent model organisms for studying development with well-characterized transcriptional networks. However, to date, nothing is known about the role of miRNAs during development in these organisms, except that the genes that are involved in the miRNA biogenesis pathway are expressed during their developmental stages. In this paper, we used Illumina Genome Analyzer (Illumina, Inc.) to sequence small RNA libraries in mixed stage population of embryos from one to three days after fertilization of sea urchin and sea star (total of 22,670,000 reads). Analysis of these data revealed the miRNA populations in these two species. We found that 47 and 38 known miRNAs are expressed in sea urchin and sea star, respectively, during early development (32 in common). We also found 13 potentially novel miRNAs in the sea urchin embryonic library. miRNA expression is generally conserved between the two species during development, but 7 miRNAs are highly expressed in only one species. We expect that our two datasets will be a valuable resource for everyone working in the field of developmental biology and the regulatory networks that affect it. The computational pipeline to analyze Illumina reads is available at http://www.benoslab.pitt.edu/services.html. © 2011 Kadri et al

Recent Advances in Σ-definability over Continuous Data Types

The purpose of this paper is to survey our recent research in computability and definability over continuous data types such as the real numbers, real-valued functions and functionals. We investigate the expressive power and algorithmic properties of the language of Sigma-formulas intended to represent computability over the real numbers. In order to adequately represent computability we extend the reals by the structure of hereditarily finite sets. In this setting it is crucial to consider the real numbers without equality since the equality test is undecidable over the reals. We prove Engeler's Lemma for Sigma-definability over the reals without the equality test which relates Sigma-definability with definability in the constructive infinitary language L_{omega_1 omega}. Thus, a relation over the real numbers is Sigma-definable if and only if it is definable by a disjunction of a recursively enumerable set of quantifier free formulas. This result reveals computational aspects of Sigma-definability and also gives topological characterisation of Sigma-definable relations over the reals without the equality test. We also illustrate how computability over the real numbers can be expressed in the language of Sigma-formulas

Developmental dynamics of sea urchin and sea star cis-regulation and the evolution of echinoderm genome organization

Trabajo presentado en EMBO Workshop The evolution of animal genomes, celebrado en modalidad virtual del 13 al 17 de septiembre de 2021

Age-related delay in information accrual for faces: Evidence from a parametric, single-trial EEG approach

Background: In this study, we quantified age-related changes in the time-course of face processing by means of an innovative single-trial ERP approach. Unlike analyses used in previous studies, our approach does not rely on peak measurements and can provide a more sensitive measure of processing delays. Young and old adults (mean ages 22 and 70 years) performed a non-speeded discrimination task between two faces. The phase spectrum of these faces was manipulated parametrically to create pictures that ranged between pure noise (0% phase information) and the undistorted signal (100% phase information), with five intermediate steps. Results: Behavioural 75% correct thresholds were on average lower, and maximum accuracy was higher, in younger than older observers. ERPs from each subject were entered into a single-trial general linear regression model to identify variations in neural activity statistically associated with changes in image structure. The earliest age-related ERP differences occurred in the time window of the N170. Older observers had a significantly stronger N170 in response to noise, but this age difference decreased with increasing phase information. Overall, manipulating image phase information had a greater effect on ERPs from younger observers, which was quantified using a hierarchical modelling approach. Importantly, visual activity was modulated by the same stimulus parameters in younger and older subjects. The fit of the model, indexed by R2, was computed at multiple post-stimulus time points. The time-course of the R2 function showed a significantly slower processing in older observers starting around 120 ms after stimulus onset. This age-related delay increased over time to reach a maximum around 190 ms, at which latency younger observers had around 50 ms time lead over older observers. Conclusion: Using a component-free ERP analysis that provides a precise timing of the visual system sensitivity to image structure, the current study demonstrates that older observers accumulate face information more slowly than younger subjects. Additionally, the N170 appears to be less face-sensitive in older observers

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30