Some statistical properties of regulatory DNA sequences, and their use in predicting regulatory regions in the Drosophila genome: the fluffy-tail test.

BACKGROUND: This paper addresses the problem of recognising DNA cis-regulatory modules which are located far from genes. Experimental procedures for this are slow and costly, and computational methods are hard, because they lack positional information. RESULTS: We present a novel statistical method, the "fluffy-tail test", to recognise regulatory DNA. We exploit one of the basic informational properties of regulatory DNA: abundance of over-represented transcription factor binding site (TFBS) motifs, although we do not look for specific TFBS motifs, per se . Though overrepresentation of TFBS motifs in regulatory DNA has been intensively exploited by many algorithms, it is still a difficult problem to distinguish regulatory from other genomic DNA. CONCLUSION: We show that, in the data used, our method is able to distinguish cis-regulatory modules by exploiting statistical differences between the probability distributions of similar words in regulatory and other DNA. The potential application of our method includes annotation of new genomic sequences and motif discovery.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Towards many colors in FISH on 3D-preserved interphase nuclei

The article reviews the existing methods of multicolor FISH on nuclear targets, first of all, interphase chromosomes. FISH proper and image acquisition are considered as two related components of a single process. We discuss (1) M-FISH (combinatorial labeling + deconvolution + widefield microscopy); (2) multicolor labeling + SIM (structured illumination microscopy); (3) the standard approach to multicolor FISH + CLSM (confocal laser scanning microscopy; one fluorochrome - one color channel); (4) combinatorial labeling + CLSM; (5) non-combinatorial labeling + CLSM + linear unmixing. Two related issues, deconvolution of images acquired with CLSM and correction of data for chromatic Z-shift, are also discussed. All methods are illustrated with practical examples. Finally, several rules of thumb helping to choose an optimal labeling + microscopy combination for the planned experiment are suggested. Copyright (c) 2006 S. Karger AG, Basel

Condensing Osteitis - Case Report

Kondenzirajući ostitis je patološko zadebljanje kosti u čeljustima, a karakteriziraju ga blagi klinički simptomi. Zadebljanje nastaje zbog poremećene pregradnje kosti, kao reakcija na blagu infekciju iz zubne pulpe. Ekstremno zadebljanje kosti lijeve strane maksile uzrokovalo je i asimetriju lica, a kliničkim te radiološkim pregledom nije se mogla postaviti konačna dijagnoza. Diferencijalno-dijagnostički, u obzir su dolazili svi tumori koštanog tkiva i cementom te kondenzirajući ostitis zbog dugotrajnog neuspješnog konzervativno-endodontskog tretmana gornjega prvog molara. Nakon kirurškog tretmana u lokalnoj anesteziji uklonjena je patološki promijenjena koštana masa i ekstrahiran zub uzročnik, jer se više nije mogao izliječiti konzervativnom terapijom. Patohistološki nalaz potvrdio je upalnu etiologiju koštane promjene. Postoperativni klinički i radiološki pregledi pokazali su potpunu sanaciju područja te koštano cijeljenje odgovarajuće gustoće i trabekularnosti. Slučaj predstavljamo kao ekstremni primjer kondenzirajućeg ostitisa zbog veličine koštane promjene, a pokazuje kako i razmjerno blaga infekcija iz zuba može prouzročiti dosta velike koštane promjene.Condensing osteitis is pathologic growth of the maxillomandibular bones, characterized by mild clinical symptoms. Bone thickening refl ects impaired bone rearrangement in response to the mild infection of dental pulp. This case report describes a patient with extreme bone thickening localized in the left maxilla causing facial asymmetry. Clinical and radiological examination failed to point to defi nitive diagnosis. On differential diagnosis, all bone tissue tumors, cementoma and condensing osteitis with prolonged unsuccessful conservative endodontic treatment of the upper fi rst molar, were considered. A surgical procedure in local anesthesia was preformed in order to remove the pathologically altered bone mass and to extract the tooth that could not have been treated successfully. Histopathologic analysis confi rmed the infl ammatory etiology of the bone lesion. Clinical and radiological follow-up indicated complete healing of the area, with appropriate density and trabeculation of the bone. This case presents as an extreme example of condensing osteitis with major bone lesion, caused by a mild tooth infection

Actual words of the year 2015

The article analyses the Russian project “Word of the Year 2015” as compared to similar Finnish and German projects. The main parameters of the most important words in literature are compared with the characteristics of the words included in the rating list of the year. The authors demonstrate that words of the year correlate with the parameters of the most popular words, but are not identical. The research defines the principles behind the formation of the Russian word list. The selection is based on expert evaluation of the frequent units of this year: this makes the resulting word list a diverse phenomenon. First, a number of lexical units of the year are united in open thematic groups which reflect those that were semantically dominant in the course of the year. Units naming the most significant events of the year also enter the list. Words of the year are a kind of trademark identity for the year, systematically reflected in vivid and recognizable units of nomination. Such markers are mainly neologisms and set expressions that have appeared as part of real situations. A special group is made up of common lexical units which get foregrounded and as a result acquire semantic increments owing to the frequency of their use and expansion of their lexical compatibility. There are two thematic groups on the 2015 list that describe the semantic dominants of the year: 1) “the foreboding of war” and 2) “the limits of the acceptable and the unacceptable”.Peer reviewe

Condensing Osteitis - Case Report

Kondenzirajući ostitis je patološko zadebljanje kosti u čeljustima, a karakteriziraju ga blagi klinički simptomi. Zadebljanje nastaje zbog poremećene pregradnje kosti, kao reakcija na blagu infekciju iz zubne pulpe. Ekstremno zadebljanje kosti lijeve strane maksile uzrokovalo je i asimetriju lica, a kliničkim te radiološkim pregledom nije se mogla postaviti konačna dijagnoza. Diferencijalno-dijagnostički, u obzir su dolazili svi tumori koštanog tkiva i cementom te kondenzirajući ostitis zbog dugotrajnog neuspješnog konzervativno-endodontskog tretmana gornjega prvog molara. Nakon kirurškog tretmana u lokalnoj anesteziji uklonjena je patološki promijenjena koštana masa i ekstrahiran zub uzročnik, jer se više nije mogao izliječiti konzervativnom terapijom. Patohistološki nalaz potvrdio je upalnu etiologiju koštane promjene. Postoperativni klinički i radiološki pregledi pokazali su potpunu sanaciju područja te koštano cijeljenje odgovarajuće gustoće i trabekularnosti. Slučaj predstavljamo kao ekstremni primjer kondenzirajućeg ostitisa zbog veličine koštane promjene, a pokazuje kako i razmjerno blaga infekcija iz zuba može prouzročiti dosta velike koštane promjene.Condensing osteitis is pathologic growth of the maxillomandibular bones, characterized by mild clinical symptoms. Bone thickening refl ects impaired bone rearrangement in response to the mild infection of dental pulp. This case report describes a patient with extreme bone thickening localized in the left maxilla causing facial asymmetry. Clinical and radiological examination failed to point to defi nitive diagnosis. On differential diagnosis, all bone tissue tumors, cementoma and condensing osteitis with prolonged unsuccessful conservative endodontic treatment of the upper fi rst molar, were considered. A surgical procedure in local anesthesia was preformed in order to remove the pathologically altered bone mass and to extract the tooth that could not have been treated successfully. Histopathologic analysis confi rmed the infl ammatory etiology of the bone lesion. Clinical and radiological follow-up indicated complete healing of the area, with appropriate density and trabeculation of the bone. This case presents as an extreme example of condensing osteitis with major bone lesion, caused by a mild tooth infection

Smoking exposure induces human lung endothelial cell adaptation to apoptotic stress

Prolonged exposure to cigarette smoking is the main risk factor for emphysema, a component of chronic obstructive pulmonary diseases (COPDs) characterized by destruction of alveolar walls. Moreover, smoking is associated with pulmonary artery remodeling and pulmonary hypertension, even in the absence of COPD, through as yet unexplained mechanisms. In murine models, elevations of intra- and paracellular ceramides in response to smoking have been implicated in the induction of lung endothelial cell apoptosis, but the role of ceramides in human cell counterparts is yet unknown. We modeled paracrine increases (outside-in) of palmitoyl ceramide (Cer16) in primary human lung microvascular cells. In naive cells, isolated from nonsmokers, Cer16 significantly reduced cellular proliferation and induced caspase-independent apoptosis via mitochondrial membrane depolarization, apoptosis-inducing factor translocation, and poly(ADP-ribose) polymerase cleavage. In these cells, caspase-3 was inhibited by ceramide-induced Akt phosphorylation, and by the induction of autophagic microtubule-associated protein-1 light-chain 3 lipidation. In contrast, cells isolated from smokers exhibited increased baseline proliferative features associated with lack of p16(INK4a) expression and Akt hyperphosphorylation. These cells were resistant to Cer16-induced apoptosis, despite presence of both endoplasmic reticulum stress response and mitochondrial membrane depolarization. In cells from smokers, the prominent up-regulation of Akt pathways inhibited ceramide-triggered apoptosis, and was associated with elevated sphingosine and high-mobility group box 1, skewing the cell's response toward autophagy and survival. In conclusion, the cell responses to ceramide are modulated by an intricate cross-talk between Akt signaling and sphingolipid metabolites, and profoundly modified by previous cigarette smoke exposure, which selects for an apoptosis-resistant phenotype

Modulation of substrate adhesion dynamics via microtubule targeting requires kinesin-1

Recent studies have shown that the targeting of substrate adhesions by microtubules promotes adhesion site disassembly (Kaverina, I., O. Krylyshkina, and J.V. Small. 1999. J. Cell Biol. 146:1033–1043). It was accordingly suggested that microtubules serve to convey a signal to adhesion sites to modulate their turnover. Because microtubule motors would be the most likely candidates for effecting signal transmission, we have investigated the consequence of blocking microtubule motor activity on adhesion site dynamics. Using a function-blocking antibody as well as dynamitin overexpression, we found that a block in dynein–cargo interaction induced no change in adhesion site dynamics in Xenopus fibroblasts. In comparison, a block of kinesin-1 activity, either via microinjection of the SUK-4 antibody or of a kinesin-1 heavy chain construct mutated in the motor domain, induced a dramatic increase in the size and reduction in number of substrate adhesions, mimicking the effect observed after microtubule disruption by nocodazole. Blockage of kinesin activity had no influence on either the ability of microtubules to target substrate adhesions or on microtubule polymerisation dynamics. We conclude that conventional kinesin is not required for the guidance of microtubules into substrate adhesions, but is required for the focal delivery of a component(s) that retards their growth or promotes their disassembly

How to measure work functions from aqueous solutions

The recent application of concepts from condensed-matter physics to photoelectron spectroscopy (PES) of volatile, liquid-phase systems has enabled the measurement of electronic energetics of liquids on an absolute scale. Particularly, vertical ionization energies, VIEs, of liquid water and aqueous solutions, both in the bulk and at associated interfaces, can now be routinely determined. These IEs are referenced to the local vacuum level, which is the appropriate quantity for condensed matter with associated surfaces, including liquids. Here, we connect this newly accessible energy level to another important surface property, namely, the solution work function, e$\Phi_{liq}$. We lay out the prerequisites for and unique challenges of determining e$\Phi$ of aqueous solutions and liquids in general. We demonstrate - for a model aqueous solution with a tetra-n-butylammonium iodide (TBAI) surfactant solute - that concentration-dependent work functions, associated with the surface dipoles generated by the segregated interfacial layer of TBA$^+$ and I$^-$ions, can be accurately measured under controlled conditions. We detail the nature of surface potentials, uniquely tied to the nature of the flowing-liquid sample, which must be eliminated or quantified to enable such measurements. This allows us to refer measured spectra of aqueous solutions to the Fermi level and quantitatively assign surfactant concentration-dependent spectral shifts to competing work function and electronic-structure effects, the latter determining, e.g., (electro)chemical reactivity. We describe the extension of liquid-jet PES to quantitatively access concentration-dependent surface descriptors that have so far been restricted to solid-phase measurements. These studies thus mark the beginning of a new era in the characterization of the interfacial electronic structure of aqueous solutions and liquids more generally.Comment: Main manuscript: 26 pages, 7 figures. Supporting information: 5 pages, 5 figure