Evolutionary diversity and developmental regulation of X-chromosome inactivation

X-chromosome inactivation (XCI) results in the transcriptional silencing of one X-chromosome in females to attain gene dosage parity between XX female and XY male mammals. Mammals appear to have developed rather diverse strategies to initiate XCI in early development. In placental mammals XCI depends on the regulatory noncoding RNA X-inactive specific transcript (Xist), which is absent in marsupials and monotremes. Surprisingly, even placental mammals show differences in the initiation of XCI in terms of Xist regulation and the timing to acquire dosage compensation. Despite this, all placental mammals achieve chromosome-wide gene silencing at some point in development, and this is maintained by epigenetic marks such as chromatin modifications and DNA methylation. In this review, we will summarise recent findings concerning the events that occur downstream of Xist RNA coating of the inactive X-chromosome (Xi) to ensure its heterochromatinization and the maintenance of the inactive state in the mouse and highlight similarities and differences between mammals

Irbesartan has a masking effect on dipyridamole stress induced myocardial perfusion defects

Background and aim The angiotensin 11 type 1 (AT(1)) receptor antagonist irbesartan is used for the treatment of hypertension, but its anti-ischaemic effect is not yet known. Our aim was to assess the effect of irbesartan administration on the diagnostic yield of Tc-99m sestamibi single photon emission computed tomography (SPECT) in patients with coronary artery disease (CAD) after dipyridamole stress

The Connection Layout in a Lattice of Four-Terminal Switches

A non classical approach to the logic synthesis of Boolean functions based on switching lattices is considered, for which deriving a feasible layout has not been previously studied. All switches controlled by the same literal must be connected together and to an input lead of the chip, and the layout of such connections must be realized in superimposed layers. Inter-layer connections are realized with vias, with the overall goal of minimizing the number of layers needed. The problem shows new interesting combinatorial and algorithmic aspects. Since the specific lattice cell where each switch is placed can be decided with a certain amount of freedom, and one literal among several may be assigned for controlling a switch, we first study a lattice rearrangement (Problem 1) and a literal assignment (Problem 2), to place in adjacent cells as many switches controlled by the same literal as possible. Then we study how to build a feasible layout of connections onto different layers using a minimum number of such layers (Problem 3). We prove that Problem 2 is NP-hard, and Problems 1 and 3 appear also intractable. Therefore we propose heuristic algorithms for the three phases that show an encouraging performance on a set of standard benchmarks