Biological activity of vanadium compounds

Vanadium compounds are characterised by a broad spectrum of action in vivo and in vitro. Their insulin-mimetic activity is manifested in their ability to normalize changes observed in both clinical and experimental diabetes (i.e. hyperglycaemia, hyperlipidaemia, lowered cell sensitivity to insulin) through the regulation of carbohydrate and lipid metabolism and the removal of secondary symptoms of this disease (as e.g. retinopathy, cardiomyopathy, nephropathy). Nevertheless, vanadium is considered to be a toxic element in both cationic and anionic form, although the latter type has more serious side effects. This is accounted for by the faster absorption of anionic forms, although the chemical structure, geometry, and the manner of synthesis of its derivatives also contributes to this elevated toxicity. Besides their antidiabetic properties, vanadium derivatives have also been observed to influence processes related to mitogenic cell responses (apoptosis, proliferation, neoplastic transformation). However, both anti-and pro-neoplastic properties of vanadium are reported.     

Biological activity of organometallic bismuth compounds

Summary The chemical aspects of organometallic bismuth(Ill) compounds are discussed with respect to the stability of the metal-carbon bond, their low dipole moments, and the limited solubility of these complexes in hydrophilic solvents. A new Bi heterocycle, which is of potential interest in terms of stability and solution behaviour, was shown to exist as an intermediate under the conditions in the mass spectrometer.Although generally bismuth organic compounds are extremely toxic, in the 1970s they became important as biocides and this is still being investigated. They have also been discussed as irritation causing chemical warfare agents. While their application in chemotherapy never became very widespread because antibiotics were discovered, in the last few years the antitumor activity of some derivatives has been reported.Abbreviations BE bond energy - IC inhibition concentration - MIC minimal inhibition concentration - electronegativity (Allred and Rochow) - X halogen, pseudohalogen=F, Cl, Br, CN - Me CH₃ - Et C₂H₅ - Bu C₄H₉ - Ph C₆H₅ - Ac CH₃COO - MS mass spectrometry     

Complementary approaches to diagnosing marine diseases: a union of the modern and the classic

Linking marine epizootics to a specific aetiology is notoriously difficult. Recent diagnostic successes show that marine disease diagnosis requires both modern, cutting-edge technology (e.g. metagenomics, quantitative real-time PCR) and more classic methods (e.g. transect surveys, histopathology and cell culture). Here, we discuss how this combination of traditional and modern approaches is necessary for rapid and accurate identification of marine diseases, and emphasize how sole reliance on any one technology or technique may lead disease investigations astray. We present diagnostic approaches at different scales, from the macro (environment, community, population and organismal scales) to the micro (tissue, organ, cell and genomic scales). We use disease case studies from a broad range of taxa to illustrate diagnostic successes from combining traditional and modern diagnostic methods. Finally, we recognize the need for increased capacity of centralized databases, networks, data repositories and contingency plans for diagnosis and management of marine disease.     

Evolutionary HMMs: a Bayesian approach to multiple alignment

MOTIVATION: We review proposed syntheses of probabilistic sequence alignment, profiling and phylogeny. We develop a multiple alignment algorithm for Bayesian inference in the links model proposed by Thorne et al. (1991, J. Mol. Evol., 33, 114-124). The algorithm, described in detail in Section 3, samples from and/or maximizes the posterior distribution over multiple alignments for any number of DNA or protein sequences, conditioned on a phylogenetic tree. The individual sampling and maximization steps of the algorithm require no more computational resources than pairwise alignment. METHODS: We present a software implementation (Handel) of our algorithm and report test results on (i) simulated data sets and (ii) the structurally informed protein alignments of BAliBASE (Thompson et al., 1999, Nucleic Acids Res., 27, 2682-2690). RESULTS: We find that the mean sum-of-pairs score (a measure of residue-pair correspondence) for the BAliBASE alignments is only 13% lower for Handelthan for CLUSTALW(Thompson et al., 1994, Nucleic Acids Res., 22, 4673-4680), despite the relative simplicity of the links model (CLUSTALW uses affine gap scores and increased penalties for indels in hydrophobic regions). With reference to these benchmarks, we discuss potential improvements to the links model and implications for Bayesian multiple alignment and phylogenetic profiling. AVAILABILITY: The source code to Handelis freely distributed on the Internet at http://www.biowiki.org/Handel under the terms of the GNU Public License (GPL, 2000, http://www.fsf.org./copyleft/gpl.html).     

Biological control of snail-borne diseases: a review

The need for alternatives to chemical control of snail-borne diseases and the growing interest in biological control methods are noted. Two groups of natural enemies of snails reviewed as especially promising for biological control are competing and predatory snails, and predatory fly larvae. Potentially useful natural enemies of the intramolluscan stages of trematodes include microsporidian infections and antagonistic trematode larvae. More unusual methods of biological control include the use of a toxic plant product (endod) and genetic manipulation of snails to decrease their susceptibility to trematode infection. The disappointing progress in biological control of snail-borne diseases in the past is attributed largely to delay in recognizing the need for alternatives to chemical control and to lack of interdisciplinary communication.     

Proteasome inhibition: a novel approach to cancer therapy

The central role of the proteasome in controlling the expression of regulators of cell proliferation and survival has led to interest in developing proteasome inhibitors as novel anticancer agents. In vitro and in vivo studies have shown that proteasome inhibitors have activity against a variety of tumor types. One of these agents, PS-341, has been tested in phase I trials in a variety of tumor types; in these trials, PS-341 treatment was well tolerated and preliminary evidence of biological activity was observed in some patients. Phase II trials in several hematological malignancies and solid tumor types are now in progress.     

A critical approach to the therapy of mitochondrial respiratory chain and oxidative phosphorylation diseases

Taking advantage of a series of questions raised by an association of patients with mitochondrial disease, this review, after a brief overview of basic concepts of mitochondrial bioenergetics and genetics, discusses the pros and cons of a number of practical options in the field of mitochondrial therapy. This makes it clear that, in contrast to the spectacular progress in our understanding of the biochemical and molecular bases of the mitochondrial diseases defined restrictively as disorders due to defects in the mitochondrial respiratory chain, we are still extremely limited in our ability to treat these conditions. We finally discussed the emerging genetic-based strategies that show some promise, even if much work remains to be done.     

Assessing the sensitivity of meta-analysis to selection bias: a multiple imputation approach

Evidence synthesis, both qualitatively and quantitatively through meta-analysis, is central to the development of evidence-based medicine. Unfortunately, meta-analysis is often complicated by the suspicion that the available studies represent a biased subset of the evidence, possibly due to publication bias or other systematically different effects in small studies. A number of statistical methods have been proposed to address this, among which the trim-and-fill method and the Copas selection model are two of the most widely discussed. However, both methods have drawbacks: the trim-and-fill method is based on strong assumptions about the symmetry of the funnel plot; the Copas selection model is less accessible to systematic reviewers, and sometimes encounters estimation problems. In this article, we adopt a logistic selection model, and show how treatment effects can be rapidly estimated via multiple imputation. Specifically, we impute studies under a missing at random assumption, and then reweight to obtain estimates under nonrandom selection. Our proposal is computationally straightforward. It allows users to increase selection while monitoring the extent of remaining funnel plot asymmetry, and also visualize the results using the funnel plot. We illustrate our approach using a small meta-analysis of benign prostatic hyperplasia.     

Liver diseases in the dish: iPSC and organoids as a new approach to modeling liver diseases

Liver diseases negatively impact the quality of life and survival of patients, and often require liver transplantation in cases that progress to organ failure. Understanding the cellular and molecular mechanisms of liver development and pathogenesis has been a challenging task, in part for the lack of adequate cellular models directly relevant to the human diseases.Recent technological advances in the stem cell field have shown the potentiality of induced pluripotent stem cells (iPSC) and liver organoids as the next generation tool to model in vitro liver diseases. Hepatocyte-like cells and cholangiocyte are currently being generated from skin fibroblasts and mononuclear blood cells reprogrammed into iPSC and have been successfully used for disease modeling, drug testing and gene editing, with the hope to be able to find application also in regenerative medicine. Protocols to generate other liver cell types are still under development, but the field is advancing rapidly. On the other end, liver cells can now be isolated from liver specimens (liver explants or liver biopsies) and cultured in specific conditions to form polarized 3D organoids. The purpose of this review is to summarize all these recent technological advances and their potential applications but also to analyze the current issues to be addressed before the technology can reach its full potential.     

Biological activity in the modern and buried soils of the St.Petersburg's historical center

Biological activity in the urban modern and medieval soils of St. Petersburg was determined using soil samples taken from sections located at the historical center of this city nearby the Kazan Cathedral, the Twelve Colleges building (now the main building of St. Petersburg State University), and on the site where the Swedish fortress Nienshants formerly existed. The studied parameters of biological activity included the microbial transformation rate of organic matter under aerobic and anaerobic conditions, the intensity of denitrification and nitrogen fixation, and the amount of microbial biomass. This investigation is the first attempt to comparatively study modern urban anthropogenically impacted soils and buried soils that had formed the soil cover of this region before St. Petersburg was founded. The major microbiological and physicochemical parameters of the soils were subjected to correlation analysis.     

SOMAP: a novel interactive approach to multiple protein sequences alignment

A novel interactive method for generating multiple protein sequencealignments is described. The program has no internal limit tothe number or length of sequences it can handle and is designedfor use with DEC VAX processors running the VMS operating system.The approach used is essentially one of manual sequence manipulation,aided by built-in symbolic displays of identities and similarities,and strict and ‘fuzzy’ (ambiguous) pattern-matchingfacilities. Additional flexibility is provided by means of aninterface to a publicly available automatic alignment systemand to a comprehensive sequence analysis package. Received on August 28, 1990; accepted on November 20, 1990     

Biological effects of selenium compounds with a particular attention to the ontogenetic development

Selenium is a trace element that is essential for living organism. Its beneficial effect is, however, expressed in a very narrow dosage range: the high and low doses of selenium are connected with pathological manifestations. The toxicity depends on the chemical form of selenium, state of organism, interactions with heavy metals and on the stage of ontogenetic development. Whereas one dose of sodium selenite (20 micromol/kg b.w.) is lethal in adult rats, suckling rats are entirely resistant. However, within one week after administration of the same dose, cataract of eye lens developed. The highest incidence of cataract was observed in 10-day-old animals and it decreased until day 20. From postnatal day 20 to day 40 the rats were resistant to both the lethal and cataractogenic effects of selenium. The incidence of cataract may be suppressed by premature weaning, lower hydration of suckling, change of water soluble/water insoluble lens protein ratio, thyroxine treatment, and by interaction with mercury. By means of its oxidative and reduction properties, selenium is involved in the maintenance of the cell redox homeostasis. Typical example is its possible cardioprotective effect: selenium decreased number of arrhythmias, reduced infarct size and improved the contractile recovery after ischemia/reperfusion injury. Selenium supplementation may thus increase cardiac tolerance to ischemic damage.     

Biological sequences integrated: a relational database approach

Over the last decade the modeling and the storage of biological data has been a topic of wide interest for scientists dealing with biological and biomedical research. Currently most data is still stored in text files which leads to data redundancies and file chaos.In this paper we show how to use relational modeling techniques and relational database technology for modeling and storing biological sequence data, i.e. for data maintained in collections like EMBL or SWISS-PROT to better serve the needs for these application domains.For this reason we propose a two step approach. First, we model the structure (and therefore the meaning of the) data using an Entity-Relationship approach. The ER model leads to a clean design of a relational database schema for storing and retrieving the DNA and protein data extracted from various sources. Our approach provides the clean basis for building complex biological applications that are more amenable to changes and software ports than their file-base counterparts.