The importance of a single primary cilium

The centrosome is the main microtubule-organizing center in animal cells, and helps to influence the morphology of the microtubule cytoskeleton in interphase and mitosis. The centrosome also templates the assembly of the primary cilium, and together they serve as a nexus of cell signaling that provide cells with diverse organization, motility, and sensory functions. The majority of cells in the human body contain a solitary centrosome and cilium, and cells have evolved regulatory mechanisms to precisely control the numbers of these essential organelles. Defects in the structure and function of cilia lead to a variety of complex disease phenotypes termed ciliopathies, while dysregulation of centrosome number has long been proposed to induce genome instability and tumor formation. Here, we review recent findings that link centrosome amplification to changes in cilium number and signaling capacity, and discuss how supernumerary centrosomes may be an important aspect of a set of cilia-related disease phenotypes

Randomized Contractions for Multiobjective Minimum Cuts

We show that Karger\u27s randomized contraction method (SODA 93) can be adapted to multiobjective global minimum cut problems with a constant number of edge or node budget constraints to give efficient algorithms. For global minimum cuts with a single edge-budget constraint, our extension of the randomized contraction method has running time tilde{O}(n^3) in an n-node graph improving upon the best-known randomized algorithm with running time tilde{O}(n^4) due to Armon and Zwick (Algorithmica 2006). Our analysis also gives a new upper bound of O(n^3) for the number of optimal solutions for a single edge-budget min cut problem. For the case of (k-1) edge-budget constraints, the extension of our algorithm saves a logarithmic factor from the best-known randomized running time of O(n^{2k} log^3 n). A main feature of our algorithms is to adaptively choose, at each step, the appropriate cost function used in the random selection of edges to be contracted. For the global min cut problem with a constant number of node budgets, we give a randomized algorithm with running time tilde{O}(n^2), improving the current best determinisitic running time of O(n^3) due to Goemans and Soto (SIAM Journal on Discrete Mathematics 2013). Our method also shows that the total number of distinct optimal solutions is bounded by O(n^2) as in the case of global min-cuts. Our algorithm extends to the node-budget constrained global min cut problem excluding a given sink with the same running time and bound on number of optimal solutions, again improving upon the best-known running time by a factor of O(n). For node-budget constrained problems, our improvements arise from incorporating the idea of merging any infeasible super-nodes that arise during the random contraction process. In contrast to cuts excluding a sink, we note that the node-cardinality constrained min-cut problem containing a given source is strongly NP-hard using a reduction from graph bisection

Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left-right asymmetry

The establishment of left–right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites—cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer’s vesicle and results in aberrant L-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia and implicate centriolar satellite–associated proteins as a new class of proteins in the pathology of L-R patterning and congenital heart disease

Survivability in hierarchical telecommunications networks under dual homing

Cataloged from PDF version of article.The motivation behind this study is the essential need for survivability in the telecommunications networks. An optical signal should find its destination even if the network experiences an occasional fiber cut. We consider the design of a two-level survivable telecommunications network. Terminals compiling the access layer communicate through hubs forming the backbone layer. To hedge against single link failures in the network, we require the backbone subgraph to be two-edge connected and the terminal nodes to connect to the backbone layer in a dual-homed fashion, i.e., at two distinct hubs. The underlying design problem partitions a given set of nodes into hubs and terminals, chooses a set of connections between the hubs such that the resulting backbone network is two-edge connected, and for each terminal chooses two hubs to provide the dual-homing backbone access. All of these decisions are jointly made based on some cost considerations. We give alternative formulations using cut inequalities, compare these formulations, provide a polyhedral analysis of the smallsized formulation, describe valid inequalities, study the associated separation problems, and design variable fixing rules. All of these findings are then utilized in devising an efficient branch-and-cut algorithm to solve this network design problem

GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program

Multiciliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate transcription and the extent to which they play redundant functions remains poorly understood. Here, we demonstrate that the transcriptional targets and proximal proteomes of GEMC1 and MCIDAS are highly similar. However, we identified distinct interactions with SWI/SNF subcomplexes; GEMC1 interacts primarily with the ARID1A containing BAF complex while MCIDAS interacts primarily with BRD9 containing ncBAF complexes. Treatment with a BRD9 inhibitor impaired MCIDAS-mediated activation of several target genes and compromised the MCC differentiation program in multiple cell based models. Our data suggest that the differential engagement of distinct SWI/SNF subcomplexes by GEMC1 and MCIDAS is required for MCC-specific transcriptional regulation and mediated by their distinct C-terminal domains

Pulmonary Embolism Revealing Idiopathic Membranous Glomerulonephritis

We describe a case of a 55-year-old man who presented with pulmonary embolism and who was found to have nephrotic syndrome due to idiopathic membranous nephropathy. There are no other signs of nephrotic syndrome such as edema

Fibrosarcome du larynx - A propos d'un cas

Le fibrosarcome du larynx est une entité histologique rare, qui représente moins de 10% de tous les sarcomes des tissus mous, moins de 2 % des cancers laryngés. Cette localisation pose des problèmes diagnostique, thérapeutique et pronostique. Nous présentons un cas de fibrosarcome laryngé chez un patient de 54 ans. La confirmation histologique etimmunohistologique a été faite sur la pièce d’exérèse chirurgicale et surtout sur une confrontation anatomoclinique. La prise en charge thérapeutique est multidisciplinaire, associant la chirurgie qui doit être la plus complète sans curage ganglionnaire et la radiothérapie. Le pronostic est généralement sévère, dépend essentiellement de degré de différenciation histologique.Mots clés : fibrosarcome ; larynx ; chirurgie ; radiothérapie

Centrosome-dependent microtubule modifications set the conditions for axon formation

Microtubule (MT) modifications are critical during axon development, with stable MTs populating the axon. How these modifications are spatially coordinated is unclear. Here, via high-resolution microscopy, we show that early developing neurons have fewer somatic acetylated MTs restricted near the centrosome. At later stages, however, acetylated MTs spread out in soma and concentrate in growing axon. Live imaging in early plated neurons of the MT plus-end protein, EB3, show increased displacement and growth rate near the MTOC, suggesting local differences that might support axon selection. Moreover, F-actin disruption in early developing neurons, which show fewer somatic acetylated MTs, does not induce multiple axons, unlike later stages. Overexpression of centrosomal protein 120 (Cep120), which promotes MT acetylation/stabilization, induces multiple axons, while its knockdown downregulates proteins modulating MT dynamics and stability, hampering axon formation. Collectively, we show how centrosome-dependent MT modifications contribute to axon formation