Single timepoint models of dynamic systems.

Many interesting studies aimed at elucidating the connectivity structure of biomolecular pathways make use of abundance measurements, and employ statistical and information theoretic approaches to assess connectivities. These studies often do not address the effects of the dynamics of the underlying biological system, yet dynamics give rise to impactful issues such as timepoint selection and its effect on structure recovery. In this work, we study conditions for reliable retrieval of the connectivity structure of a dynamic system, and the impact of dynamics on structure-learning efforts. We encounter an unexpected problem not previously described in elucidating connectivity structure from dynamic systems, show how this confounds structure learning of the system and discuss possible approaches to overcome the confounding effect. Finally, we test our hypotheses on an accurate dynamic model of the IGF signalling pathway. We use two structure-learning methods at four time points to contrast the performance and robustness of those methods in terms of recovering correct connectivity.

Learning cyclic signaling pathway structures while minimizing data requirements.

Bayesian network structure learning is a useful tool for elucidation of regulatory structures of biomolecular pathways. The approach however is limited by its acyclicity constraint, a problematic one in the cycle-containing biological domain. Here, we introduce a novel method for modeling cyclic pathways in biology, by employing our newly introduced Generalized Bayesian Networks (GBNs). Our novel algorithm enables cyclic structure learning while employing biologically relevant data, as it extends our cycle-learning algorithm to permit learning with singly perturbed samples. We present theoretical arguments as well as structure learning results from realistic, simulated data of a biological system. We also present results from a real world dataset, involving signaling pathways in T-cells.

Measurement of spin-transfer observables in p p-->Lambda Lambda at 1.637 GeV/c.

Spin-transfer observables for p p-->Lambda Lambda have been measured using a transversely polarized frozen-spin target and a beam momentum of 1.637 GeV/c. Current models of the reaction near threshold are in good agreement with existing measurements performed with unpolarized particles in the initial state but produce conflicting predictions for the spin-transfer observables Dnn and Knn (the normal-to-normal depolarization and polarization transfer), which are measurable only with polarized target or beam. Measurements of Dnn and Knn presented here are found to be in disagreement with predictions from these models.

Assays for activation of opsin by all-trans-retinal.

The data collected with the techniques discussed in this chapter suggest significant differences between the active conformation(s) of the opsin/atr complex, which are reversibly formed in the dark, and the active conformation (R*) of the meta-II photoproduct. First, there is good evidence for noncovalent opsin/atr complexes with considerable activity (although covalent binding of atr is found in mutant opsins. Even more intriguing, all-trans-retinal in an amount that saturates the activity of the opsin/atr complex toward Gt does not measurably inhibit the access of 11-cis-retinal to the light-sensitive binding site during regeneration (Fig. 2C). On the other hand, forced protonation at or near Glu-134 appears to be an integral mechanism for both the meta-II and the opsin-like activities (Fig. 4). Thus, it is not inconceivable that these two activities of the receptor arise from two fundamentally different conformations, one meta-II-like and one opsin-like. They would be similar with respect to the Gt (or RK) protein-protein interaction but different in their mode of retinal-protein interaction.

Diffusible ligand all-trans-retinal activates opsin via a palmitoylation-dependent mechanism.

In rhodopsin's function as a photoreceptor, 11-cis-retinal is covalently bound to Lys(296) via a protonated Schiff base. 11-cis/all-trans photoisomerization and relaxation through intermediates lead to the metarhodopsin II photoproduct, which couples to transducin (G(t)). Here we have analyzed a different signaling state that arises from noncovalent binding of all-trans-retinal (atr) to the aporeceptor opsin and enhances the very low opsin activity by several orders of magnitude. Like with metarhodopsin II, coupling of G(t) to opsin-atr is sensitive to competition by synthetic peptides from the COOH termini of both G(t)alpha and G(t)gamma. However, atr does not compete with 11-cis-retinal incorporation into the Lys(296) binding site and formation of the light-sensitive pigment. Blue light illumination fails to photorevert opsin-atr to the ground state. Thus noncovalently bound atr has no access to the light-dependent binding site and reaction pathway. Moreover, in contrast to light-dependent signaling, removal of the palmitoyl anchors at Cys(322) and Cys(323) in the rhodopsin COOH terminus impairs the atr-stimulated activity. Repalmitoylation by autoacylation with palmitoyl-coenzyme A restores most of the original activity. We hypothesize that the palmitoyl moieties are part of a second binding pocket for the chromophore, mediating hydrophobic interactions that can activate a large part of the catalytic receptor/G-protein interface.

Palmitoylation of rhodopsin with S-protein acyltransferase: enzyme catalyzed reaction versus autocatalytic acylation.

Protein palmitoylation in vitro was studied using bovine rhodopsin as the substrate and a partially purified acylating enzymatic activity (PAT) from placental membranes. PAT incorporates fatty acid into rhodopsin with higher efficiency (10 times higher initial rate), as compared to autoacylation. The activity is sensitive to heat and trypsin, indicating a protein-mediated enzymatic process and requires the native conformation of rhodopsin. The presence of deacylated, free cysteine residues in dark-adapted rhodopsin increases palmitoylation via PAT. The sites for non-enzymatic and enzymatic palmitoylation could not be distinguished by peptide mapping. The reversible palmitoylation described here will provide a tool for the study of the role of palmitoylation in photoreceptor function.

Nutrition for in-home AIDS patients.

Early medical nutrition intervention with in-home AIDS patients can help prolong and improve the quality and quantity of their lives. Teaching the basics of good nutrition both early on as well as in the later stages of AIDS can save thousands of health care dollars through preventive care at home.

[Influence of bacterial infection and formalin vapors on the course of ovalbumin induced experimental bronchospastic reaction in guinea pigs]. / Wplyw zakazenia bakteryjnego i par formaliny na przebieg wywolanych doswiadczalnie stanów bronchospastycznych u swinek morskich.

The pathomechanism of the bronchospastic reaction is not fully explained. Ovalbumin induced bronchospastic reaction in guinea pigs is widely accepted as a classical experimental model and was appleid in this study. The bronchoconstriction, bronchial hypersensitivity and humoral immune response were measured after bronchial infection and chemical injury by formalin vapours. The intensity of the bronchospasm was measured by Lundberg index, the haemolytic activity of complement and the level of circulating immune complexes were measured at the beginning and at the end of the experiment. The increase of the bronchospastic reaction and bronchial hypersensitivity was observed bacterial infection and after formalin vapours too. Bronchial infection and chemical irritation of bronchial tree lead to the increase of the circulating immune complexes level and to the decrease of the haemolytic activity of the complement.

[Histology of the respiratory system after exposure to bacterial infection and formalin vapors used to induce experimental bronchospasm]. / Obraz histologiczny struktur ukladu oddechowego po ekspozycji na zakazenia bakteryjne i pary formaliny wywolujace doswiadczalny model skurczu oskrzeli.

The purpose of the research was to observe the influence of the bacterial infection and inhalation vapours on the histologic picture of bronchi and lungs in the course on the experimental asthma induced in guinea pigs. The animals were divided into 6 groups. The animals were immunized by ovalbumin. Group I was control and was subjected to inhalations of physiologic salt solutions. Group II was immunized by the soluble of ovalbumin intraperitoneally and was inhaled with the solution of ovalbumin. Group III was subjected only to inhalation of the ovalbumin. Group IV was inhaled with the solution of formalin alternately. Group V experienced only formalin inhalations. Group VI was infected with Pseudomonas aeruginosa strain and inhaled with the solution of ovalbumin. On the histologic examination of the lung tissue the authors found the atrophy of the lymphatic system, the hypertrophy of the mucous membrane and muscular coat of the bronchi, the accumulation of large amount of mucus in their lumen and the exfoliation of the bronchial epithelium.

[Influence of bacterial infection during ovalbumin induced experimental asthma in guinea pigs]. / Wplyw zakazenia bakteryjnego na przebieg doswiadczalnej astmy indukowanej owalbumina u swinek morskich.

The pathomechanism of bronchial asthma is not fully explained. The immunologic reactions in the bronchial epithelium may be better understood by an experimental approach in laboratory animals. Ovalbumin induced asthma in guinea pigs is widely accepted as an experimental model of bronchial asthma and was applied in this study. The bronchoconstriction, bronchial hypersensitivity and humoral immune response were measured after bronchial infection (intranasal Pseudomonas aeruginosa application). The increase of the bronchospastic reaction and bronchial hypersensitivity was observed after intranasal Pseudomonas aeruginosa application. Bacterial infection lead to the increase of the circulating immune complexes level and to the decrease of the haemolytic activity of the complement in serum.

[Behavior of some parameters of the autonomic nervous system in patients with bronchial asthma]. / Zachowanie sie niektórych parametrów ukladu autonomicznego u chorych na astme oskrzelowa.

It is well known that beta receptors play a crucial role in maintaining tonus of smooth muscles of the airways. In this study the authors have indirectly assessed the beta receptor performance by measuring serum cAMP levels before and after intravenous administration of Salbutamol. Parallelly the activity of the parasympathetic system was analysed. The observed increases of serum cAMP dependent on different duration of the disease. The age of the patients did not affect the observations. These results may imply that disturbances of beta-2 receptors function are acquired in patients with bronchial asthma.

Absorption and accumulation of cadmium, lead and mercury from foods by rats.

The purpose of this study was to estimate the apparent absorbability of cadmium (Cd), lead (Pb) and mercury (Hg) from different foods by young rats when these elements occur intrinsically. The study consisted of three independent experiments. In the first experiment rats were fed a casein control diet, a corn-silage diet or an activated-sludge diet. Although the amount of Cd, Pb and Hg ingested from the sludge diet was orders of magnitude higher than that from the casein or corn-silage diet, the absorption of the metals was significantly less (P < 0.02) because these were present as poorly-soluble phosphates. In the second experiment, rats were fed either a commercial fish-meal control diet or an experimental fish-meal diet, with or without the addition of sodium phytate, based on catches from metal-polluted waters. No reduction in absorption resulted from the diet containing phytate as compared with the diet without phytate. The third experiment used the radioactive tracers Cd-115m, Pb-210 and Hg-203 intrinsically incorporated individually into maturing corn ears, on which the three experimental diets were based. The liver and kidney were the main target organs for all three elements (liver: Cd 0.6%, Pb 1.4% and Hg 0.6%; kidney: Cd 0.8%, Pb 0.9% and Hg 1.3%).

Use of cisplatin, cyclophosphamide, vincristine, and doxorubicin for the treatment of non-small cell lung cancer.

Forty-four evaluable patients with non-small cell carcinoma of the lung were treated with cisplatin, cyclophosphamide, vincristine, and doxorubicin. The overall response rate was 57%. The 16% who had complete response had a median survival of 81 weeks.

The athletic polydrug abuse phenomenon. A case report.

A case of a power weight lifter who is ingesting large doses of anabolic steroids plus other drugs to counteract their short-term side effects is presented. This type of polydrug abuse phenomenon which is unique to the competitive athlete is widespread despite the lack of convincing evidence that anabolic steroids increase muscular strength. The vast extent of this drug abuse problem is poorly appreciated by the general medical community. The potential complications of the long-term usage of these drugs such as liver failure, hepatocellular carcinoma, and peliosis hepatitis make these drugs extremely dangerous.