World-Volume Locally Supersymmetric Born-Infeld Actions

We derive manifestly locally supersymmetric extensions of the Born-Infeld action with $p=2$. The construction is based on a first order bosonic action for $Dp$-branes with a generalized Weyl invariance.Comment: LaTeX, 14 pages, typos corrected, references and some remarks adde

Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10$^{−27and−30}$). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research

Electrotonic Signals along Intracellular Membranes May Interconnect Dendritic Spines and Nucleus

Synapses on dendritic spines of pyramidal neurons show a remarkable ability to induce phosphorylation of transcription factors at the nuclear level with a short latency, incompatible with a diffusion process from the dendritic spines to the nucleus. To account for these findings, we formulated a novel extension of the classical cable theory by considering the fact that the endoplasmic reticulum (ER) is an effective charge separator, forming an intrinsic compartment that extends from the spine to the nuclear membrane. We use realistic parameters to show that an electrotonic signal may be transmitted along the ER from the dendritic spines to the nucleus. We found that this type of signal transduction can additionally account for the remarkable ability of the cell nucleus to differentiate between depolarizing synaptic signals that originate from the dendritic spines and back-propagating action potentials. This study considers a novel computational role for dendritic spines, and sheds new light on how spines and ER may jointly create an additional level of processing within the single neuron

Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research

The transition from dendrite to soma compels the VE to converge at the soma.

<p>(A) The soma is characterized by a wider diameter and the presence of the cell nucleus. The nucleus is enclosed by two nuclear envelopes (<i>NE</i>) and occupies the majority of the cell's cross-section, at its widest diameter. The outer NE is continuous with the ER membrane and the space between the two NE is continuous with the ER lumen (<i>ER lumen</i>). The NE allows continuity between the nucleoplasm and the cytosol through pore complexes (<i>P</i>), ∼9 nm in diameter. Altogether, the structure of the nucleoplasm and the two nuclear envelopes establishes an electrical continuity with the inner cable. Thus, the electrotonic pathway from the dendritic spine to the cell nucleus may be reduced to three successive CIC systems as indicated by three grey rectangles: (a) dendritic-CIC, (b) perinuclear-CIC and (c) nuclear-CIC. (B) A simplified simulation of the transition from dendrites to soma was conducted by connecting a dendritic-CIC (labeled ‘a’) with somatic-CIC (labeled ‘b’ and ’c’). The dendritic-CIC followed the default parameters (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000036#pcbi-1000036-t002" target="_blank">Table 2</a>), whereas the somatic-CIC had a wider diameter (<i>d</i>_mP = 16 µm) and was further divided into two consecutive segments: perinuclear zone (labeled ‘b’) and nuclear zone (labeled ‘c’). The perinuclear-zone was short (0.2 λ) and characterized by a narrow cytosolic cross-section and wide ER cross-section (<i>E</i> = 0.99) and the nuclear-zone was characterized by a wide non-conductive cross-section (<i>N</i> = 0.9 and the original <i>E</i> value, <i>E</i> = 0.45). (C) <i>V</i>_mE traces of two spatially distinct synaptic sources (red and blue traces) separated by a distance of 0.2 electrotonic units, are plotted with and without the effect of the somatic-CIC (solid and dashed lines, respectively). Each trace is scaled to the EPSP amplitude at the VE-peak (nVE). Right: Vertical expansion into the region of transition from dendritic-CIC to somatic-CIC (shaded zone). The triangles mark the origin (i.e. synaptic source) of each curve by corresponding colors. Note that at the segment that follows the transition from a dendritic-CIC into a somatic-CIC, both traces, which are otherwise negative, become positive and the VE peaks reach higher levels.</p