Formal Methods for Hopfield-Like Networks

Building a meaningful model of biological regulatory network is usually done by specifying the components (e.g. the genes) and their interactions, by guessing the values of parameters, by comparing the predicted behaviors to the observed ones, and by modifying in a trial-error process both architecture and parameters in order to reach an optimal fitness. We propose here a different approach to construct and analyze biological models avoiding the trial-error part, where structure and dynamics are represented as formal constraints. We apply the method to Hopfield-like networks, a formalism often used in both neural and regulatory networks modeling. The aim is to characterize automatically the set of all models consistent with all the available knowledge (about structure and behavior). The available knowledge is formalized into formal constraints. The latter are compiled into Boolean formula in conjunctive normal form and then submitted to a Boolean satisfiability solver. This approach allows to formulate a wide range of queries, expressed in a high level language, and possibly integrating formalized intuitions. In order to explore its potential, we use it to find cycles for 3-nodes networks and to determine the flower morphogenesis regulatory network of Arabidopsis thaliana. Applications of this technique are numerous and concern the building of models from data as well as the design of biological networks possessing specified behaviors.     

Zur Ultrastruktur des Hypophysen-Zwischenhirnsystems der Ratte

Zusammenfassung Die Ergebnisse elektronenmikroskopischer Untersuchungen an den großzelligen Kerngebieten des Zwischenhirns von Ratten, die unter normalen und experimentellen Bedingungen gehalten wurden, lassen sich wie folgt zusammenfassen:Das granuläre Retikulum (Nissl-Substanz) unterscheidet sich nicht von dem anderer Neurone. Nach Belastung kommt es zu einer Zunahme der freien und membrangebundenen Ribosomen. Eine Abnahme der Cytoplasma-RNS nach längerer Belastung ist als Zeichen der Erschöpfung zu deuten.Das agranuläre Retikulum (Golgikomplex) bildet in den Perikaryen normaler Tiere ein kontinuierliches Membransystem, das den perinukleären Bereich gegen die Peripherie abgrenzt. Nach Belastung kommt es zu einer Desintegration dieses Membransystems.In unmittelbarer Nachbarschaft der Golgi-Membranen sind zahlreiche Bläschen unterschiedlicher Göße und Dichte zu beobachten, die als Prosekretvakuolen gedeutet werden.Nach Belastung kann eine Zunahme des agranulären auf Kosten des granulären Retikulum erfolgen. Dieser Befund entspricht der auf lichtmikroskopische Beobachtungen gestützten Annahme Bargmanns, daß Neurosekret auf Kosten der Nissl-Substanz gebildet wird.Elementar- bzw. Neurosekretgranula sind in den Axonen im allgemeinen reichlicher vorhanden als in den Perikaryen, doch können diese unter bestimmten Bedingungen auch in den Perikaryen in großer Anzahl vorkommen.Es wird angenommen, daß die aus dem Golgikomplex stammenden Prosekretvakuolen sowohl in den Perikaryen als auch in den Axonen zu Elementargranula transformiert werden können.

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Summary Electron microscopic investigations of the magnocellular nuclei of the diencephalon of rats kept under normal and experimental conditions render the following results: No difference is found between their Nissl substance and that of other neurons. As a result of stress an increase of free and membrane bound ribosomes is observed. A decrease in cytoplasmic RNA after a long-lasting stress situation seems to indicate a state of exhaustion. In normal animals the Golgi apparatus forms a continous membrane system in the perikarya, that separates the perinuclear region from the periphery. In stressed animals this membrane system shows signs of disintegration. — Numerous vesicles of varying size and density are observed in the immediate vicinity of the Golgi membranes; they are regarded as pre-secretory vacuoles. It is possible that in a stress situation the agranular reticulum is increased at the expense of the granular reticulum. This observation is in agreement with Bargmann's lightmicroscopical findings according to which neurosecretory substance is formed at the expense of Nissl substance. On the whole more neurosecretory granules are found in the axons than in the perikarya. Under certain conditions, however, they are also found in great numbers as well as the in the perikarya. It is postulated that in the perikarya axons the pre-secretory vacuoles originating from the Golgi apparatus, are transformed into neurosecretory granules.

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Eva-Maria Finze und Maria Widuch danke ich für wertvolle technische Hilfe.

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Durchgeführt mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

<Emphasis Type="Italic">Marinobacter piscensis</Emphasis> sp. nov., a Moderately Halophilic Bacterium Isolated from Salty Food in Tunisia

An aerobic, Gram-negative, moderately halophilic bacterium, oxidase, and catalase positive-designated Abdou3^T, was isolated from salted traditional foods (Anchovies) in Tunisia. Cells were rod-shaped, non-spore-forming and motile. Growth occurred at 15–45 °C (optimum, 37 °C), pH 5.5–8.75 (optimum, 7.3), and in the presence of 1–15 % NaCl (optimum, 10 %). Strain Abdou3^T used glucose, d-arabinose, and sucrose. Strain Abdou3^T had Q9 as the major respiratory quinone and C_18:1 ω9c and C_16:0 as predominant fatty acids. The DNA G+C content was 55.2 mol%. Phylogenetic analysis of the small-subunit ribosomal RNA (rRNA) gene sequence indicated that strain Abdou3^T had as its closest relative Marinobacter maritimus (identity of 96 %). Based on phenotypic, phylogenetic, and taxonomic characteristics, strain Abdou3^T is proposed as a novel species of the genus Marinobacter within the order Alteromonadales, for which the name M. piscensis sp. nov. is proposed. The type strain is Abdou3^T (=DSM 26804^T).     

MCP-1 −2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients

Monocyte chemoattractant protein-1 (MCP-1) plays crucial role in protective immunity against Mycobacterium tuberculosis (MT). In this study, we examined whether single nucleotide polymorphism (SNP) −2518 A/G (rs 1024611) of MCP-1 affect the susceptibility to active tuberculosis (TB) in Tunisian populations. Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1 −2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that −2518 G allele and GG genotype (high MCP-1 producer) frequencies were significantly more elevated in active pulmonary TB group in comparison to control group [34 vs. 22%; P = 0.0007; 15 vs. 5%, P corrected for the number of genotypes (Pc) = 0.015; respectively]. Additionally, they were associated with increased risk development of this clinical form of TB [odds ratio (OR) = 1.83, 95% confidence intervals (CI) = 1.26–2.66; OR = 3.1, 95% CI = 1.28–7.76; respectively]. However, wild type allele −2518 A and AA genotype were over-represented in control group (78 and 62%) and seem to be protective factors against TB. Moreover, −2518 AA genotype was more frequent in control group and was associated with resistance against development of active pulmonary TB (OR = 0.56, 95% CI = 0.35–0.89, Pc = 0.03). Our findings confirm the key role of −2518 A/G SNP of MCP-1 and support its association with resistance/susceptibility to the development of active pulmonary TB in the Tunisian population.     

Species Composition of Saproxylic Fungal Communities on Decaying Logs in the Boreal Forest

Coarse woody debris supports large numbers of saproxylic fungal species. However, most of the current knowledge comes from Scandinavia and studies relating the effect of stand or log characteristics on the diversity and composition of decomposer fungi have not been conducted in Northeastern Canada. Logs from five tree species were sampled along a decomposition gradient in nine stands representing three successional stages of the boreal mixed forest of Northwestern Quebec, Canada. Using a molecular fingerprinting technique, we assessed fungal community Shannon–Weaver diversity index, richness, and composition. We used linear mixed models and multivariate analyses to link changes in fungal communities to log and stand characteristics. We found a total of 33 operational taxonomic units (OTUs) including an indicator species for balsam fir (similar to Athelia sp.) and one found only in aspen stands (similar to Calocera cornea). Spruce logs supported the highest fungal Shannon–Weaver diversity index and OTU number. Our results support the hypothesis that log species influences fungal richness and diversity. However, log decay class does not. Stand composition, volume of coarse woody debris, and log chemical composition were all involved in structuring fungal communities. Maintaining the diversity of wood-decomposing communities therefore requires the presence of dead wood from diverse log species.     

Antidepressant-warfarin interaction and associated gastrointestinal bleeding risk in a case-control study

BackgroundBleeding is the most common and worrisome adverse effect of warfarin therapy. One of the factors that might increase bleeding risk is initiation of interacting drugs that potentiate warfarin. We sought to evaluate whether initiation of an antidepressant increases the risk of hospitalization for gastrointestinal bleeding in warfarin users.Conclusions/SignificanceWarfarin users who initiated citalopram, fluoxetine, paroxetine, amitriptyline, or mirtazapine had an increased risk of hospitalization for gastrointestinal bleeding. However, the elevated risk with mirtazapine suggests that a drug-drug interaction may not have been responsible for all of the observed increased risk.     

Characterization of Halanaerobaculum tunisiense gen. nov., sp. nov., a new halophilic fermentative, strictly anaerobic bacterium isolated from a hypersaline lake in Tunisia

A new halophilic anaerobe was isolated from the hypersaline surface sediments of El-Djerid Chott, Tunisia. The isolate, designated as strain 6SANG, grew at NaCl concentrations ranging from 14 to 30%, with an optimum at 20–22%. Strain 6SANG was a non-spore-forming, non-motile, rod-shaped bacterium, appearing singly, in pairs, or occasionally as long chains (0.7–1 × 4–13 μm) and showed a Gram-negative-like cell wall pattern. It grew optimally at pH values between 7.2 and 7.4, but had a very broad pH range for growth (5.9–8.4). Optimum temperature for growth was 42°C (range 30–50°C). Strain 6SANG required yeast extract for growth on sugars. Glucose, sucrose, galactose, mannose, maltose, cellobiose, pyruvate, and starch were fermented. The end products from glucose fermentation were acetate, butyrate, lactate, H₂, and CO₂. The G + C ratio of the DNA was 34.3 mol%. Strain 6SANG exhibited 16S rRNA gene sequence similarity values of 91–92% with members of the genus Halobacteroides, H. halobius being its closest phylogenetic relative. Based on phenotypic and phylogenetic characteristics, we propose that this bacterium be classified as a novel species of a novel genus, Halanaerobaculum tunisiense gen. nov., sp. nov. The type strain is 6SANG^T (=DSM 19997^T = JCM 15060^T).     

Different patterns of cytokeratin expression in the normal epithelia of the upper respiratory tract

The distribution and type of cytokeratins present in the normal human epithelia of the nasopharynx, oropharynx, tongue, palatine tonsil, epiglottis, vocal cord, and laryngeal ventricle were studied using immunohistochemical techniques and by gel electrophoresis of cytoskeletal proteins microdissected from frozen tissues. Noncornifying stratified epithelia covering the oropharynx, tongue, surface of the palatine tonsil, pharyngeal surface of the epiglottis, and vocal cord were all found to contain cytokeratins nos. 4, 5, 6, 13, 14, and 15, together with minor amounts of cytokeratin no. 19, i.e., a pattern similar to that previously reported for esophageal epithelium. The immunohistochemical reaction with KA4, an antibody specific for cytokeratins nos. 14, 15, 16, and 19, revealed reactivity confined to the basal epithelial cells of the tongue, oropharynx, pharyngeal epiglottis, and two out of five samples of vocal cords. This same antibody reacted with the entire thickness of three out of the five true vocal cords which were shown by gel electrophoresis to also contain cytokeratins nos. 16 and 17. Gel electrophoresis revealed that the pseudostratified columnar epithelium covering the laryngeal ventricle was more complex, in that it contained cytokeratins nos. 5, 13, 14, 15, and 17, which are typical of stratified epithelia, as well as cytokeratins nos. 7, 8, 18, and 19, which are characteristic of simple epithelia. This pattern is similar to that found in bronchial epithelium. The laryngeal surface of the epiglottis exhibited cytokeratins nos. 4, 5, 7, 8, 13, 14, 15, 17, 18, and 19, i.e., a pattern combining features of both esophageal- and bronchial-type epithelia. The reaction of these epithelia containing columnar cells with antibody RGE-53, which is specific for cytokeratin no. 18, revealed a staining reaction confined to the superficial columnar cells, whereas KA1 stained only the basal cells of these epithelia. The results of our study make it possible to distinguish two types of noncornifying stratified squamous epithelium, namely the 'esophageal type' which covers the tongue, oropharynx, and pharyngeal surface of the epiglottis, and another type which overlies the vocal cords and the transitional zone between the pharyngeal and laryngeal surfaces of the epiglottis. Furthermore, there appear to be variants of pseudostratified columnar epithelium, i.e., the usual bronchial type lining the laryngeal ventricle, and a type with a thicker subcolumnar cell compartment that is found on the laryngeal surface of the epiglottis. The patterns of expression of cytokeratins in the respiratory tract are compared with those of other epithelia.