Potential applications of viable,immobilized fungal cell systems

Immobilized cell technology attracts considerable attention because of the many advantages it offers over conventional suspended-cell fermentations. Important advances continue to be made in the potential use of immobilized cells as biocatalysts. This review is mainly devoted to the analysis of recent literature on the applications of immobilized fungal cell systems, ranging from the production or transformation of useful compounds (e.g. organic acids, enzymes, antibiotics, steroids, etc.) to wastewater treatment. The problems and future industrial applications are also discussed.Based on an invited lecture presented at the Convegno RAISA on Sistemi Biologici Immobilizati in Bologna, Italy, on 3 to 4 November 1992.     

Exploiting marine actinomycete biosynthetic pathways for drug discovery

Drug discovery relies on the generation of large numbers of structurally diverse compounds from which a potential candidate can be identified. To this end, actinomycetes have often been exploited because of their ability to biosynthesize an impressive array of novel metabolites particularly polyketides. The genetic organization of polyketide synthases (PKSs) makes them readily amenable to manipulation, and thus re-engineering artificial or hybrid PKSs to produce unnatural natural products is a reality. This review highlights two approaches we have used to generate novel polyketides by manipulating genes responsible for starter unit biosynthesis in the Streptomyces maritimus enterocin type II PKS. Our preliminary investigation into the biosynthesis of neomarinone, a rare marine actinomycete-derived meroterpenoid, is also presented.     

Vertebrate Crystallins--from Proteins to Genes

A review of literature on tissue-specific proteins of the vertebrate eye lens and genes coding for these proteins is presented. Particular attention is paid to the most heterogeneous family of crystallins: - and -crystallins, their nomenclature, and the structure of their genes. It is pointed out that mutations in gene coding for ubiquitous crystallins may be related to some forms of cataracts.     

Neglected Consequences: Role of Introduced Aquatic Species in the Spread of Infectious Diseases

Introduction of aquatic organisms to new ecosystems has led to massive alterations to the structure and function of natural ecosystems, and to extinction of native flora and fauna. The ecological impacts caused by exotic aquatic species worldwide have been widely recognized, but the past and potential human health impacts of these introductions have been largely ignored. This review identifies several modes by which introduced aquatic species negatively impact human health: a) the direct introduction of human pathogens and/or their hosts; b) the introduction of pathogens of species upon which humans depend; and c) structural and functional alterations of ecosystems that affect other aquatic species upon which humans depend. The literature review presented here focuses on the first of these modes, presenting examples of either pathogens or hosts of pathogens (or both) that are documented to have been introduced, and that either affect or have the potential to affect human health, and occur in aquatic environments. Documented or suspected cases of introduced species that have caused human health impacts include: a) introduced dinoflagellates, which cause the accumulation of human neurotoxins in shellfish; b) various species of freshwater snails hosting a variety of human disease organisms, including Schistosoma mansoni (the cause of intestinal schistosomiasis), schistosomes that cause swimmers itch (cercarial dermatitis), the liver fluke Fasciola hepatica, and others; c) Vibrio cholerae, the agent of infection of cholera disease; and d) introduced mitten crabs, which can carry a human lung fluke.     

The morphology of human blood platelets and the coagulation of human blood in vitro

Summary A review of the electron-microscopical work on blood platelets is given. A number of electron-micrographs are presented showing normal as well as disintegrating blood platelets and their participation in the formation of the blood clot.This work was aided by a grant from the Foundation Therese och Johan Anderssons Minne, Stockholm, Sweden.     

Cancer biomarker discovery and translation: proteomics and beyond

Introduction: Cancer is often diagnosed at late stages when the chance of cure is relatively low and although research initiatives in oncology discover many potential cancer biomarkers, few transition to clinical applications. This review addresses the current landscape of cancer biomarker discovery and translation with a focus on proteomics and beyond.

Areas covered: The review examines proteomic and genomic techniques for cancer biomarker detection and outlines advantages and challenges of integrating multiple omics approaches to achieve optimal sensitivity and address tumor heterogeneity. This discussion is based on a systematic literature review and direct participation in translational studies.

Expert commentary: Identifying aggressive cancers early on requires improved sensitivity and implementation of biomarkers representative of tumor heterogeneity. During the last decade of genomic and proteomic research, significant advancements have been made in next generation sequencing and mass spectrometry techniques. This in turn has led to a dramatic increase in identification of potential genomic and proteomic cancer biomarkers. However, limited successes have been shown with translation of these discoveries into clinical practice. We believe that the integration of these omics approaches is the most promising molecular tool for comprehensive cancer evaluation, early detection and transition to Precision Medicine in oncology.     

Phloem unloading and ‘sink strength’: The parallel between the site of attachment of Cuscuta and developing legume seeds

Sink regions play a central role in determining assimilate distribution patterns. Two factors are discussed which have a strong effect on the sink strength of a sink, viz. phloem unloading and turgor-sensitive transport. Sink strength may be defined as the capacity of phloem in the sink region to import assimilates from other parts of the plants and to release the imported substances into the sink apoplast.A stem parasitized by Cuscuta represents a very strong sink. A review is presented of data on enhanced phloem unloading, at the site of attachment of Custuta. Recent data on metabolically controlled sucrose and amino acid unloading into the seed coat apoplast of developing legume seeds show a remarkable parallel with phloem unloading in a parasitized Vicia faba stem. Data on turgor-sensitive sucrose and amino acid transport into developing seeds are presented, which throw new light on the pressure flow theory of phloem transport.     

MSCs and hyaluronan: Sticking together for new therapeutic potential?

Research involving mesenchymal multipotent/stem/progenitor/stromal/marrow cells (MSCs) have translated to clinical trials at an extraordinary pace. By the time of this review, the public clinical trials database (http://clinicaltrials.gov) has 394 clinical trials listed using MSCs for a very wide range of therapeutic applications. Unexpectedly, the explanation for the increase in clinical trials using MSCs does not lie on a well-defined therapeutic mechanism – dramatic results have been demonstrated in a variety of studies involving different animal models of diseases, often describing discrete therapeutic mechanisms exerted by MSCs. This review will focus on recent data suggesting the involvement of hyaluronic acid (HA) in the beneficial effects of MSCs, evaluate the potential of MSC as modulators of HA and the implications of this modulation for disease therapy.     

Occurrence of lignin degradation genotypes and phenotypes among prokaryotes

A number of prokaryotes actively contribute to lignin degradation in nature and their activity could be of interest for many applications including the production of biogas/biofuel from lignocellulosic biomass and biopulping. This review compares the reliability and efficiency of the culture-dependent screening methods currently used for the isolation of ligninolytic prokaryotes. Isolated prokaryotes exhibiting lignin-degrading potential are presented according to their phylogenetic groups. With the development of bioinformatics, culture-independent techniques are emerging that allow larger-scale data mining for ligninolytic prokaryotic functions but today, these techniques still have some limits. In this work, two phylogenetic affiliations of isolated prokaryotes exhibiting ligninolytic potential and laccase-encoding prokaryotes were determined on the basis of 16S rDNA sequences, providing a comparative view of results obtained by the two types of screening techniques. The combination of laboratory culture and bioinformatics approaches is a promising way to explore lignin-degrading prokaryotes.     

Investigation of the relation between structure and function in myelinated nerve fibres with the aid of ultraviolet radiation

Ultraviolet radiation induces two photochemical alterations relevant to excitability in the nodal membranes: A selective blocking of the sodium permeability and a potential translation of the voltage dependent kinetic parameters of sodium inactivation and activation along the potential axis in the negative direction. The underlying processes are two different photoreactions, since 1) the action spectrum of the blocking effect shows a marked peak near 280 nm and rapidly decreasing sensitivity towards higher and lower wavelengths, while the action spectrum of the potential shift increases with lower wavelengths; 2) the blocking effect is enhanced by a more positive holding potential, while the potential shift is decreased; 3) the potential shift can be prevented intraaxonal application of l-cysteine or 2-mercaptoethanol, but the blocking effect is not affected.Paper presented at the Biomembrane Symposium of the Deutsche Gesellschaft für Biophysik, Freiburg, April 1975.     

Recent advances in the metabolomic study of bladder cancer

Introduction: Metabolomics is a chemical process, involving the characterization of metabolites and cellular metabolism. Recent studies indicate that numerous metabolic pathways are altered in bladder cancer (BLCA), providing potential targets for improved detection and possible therapeutic intervention. We review recent advances in metabolomics related to BLCA and identify various metabolites that may serve as potential biomarkers for BLCA.

Areas covered: In this review, we describe the latest advances in defining the BLCA metabolome and discuss the possible clinical utility of metabolic alterations in BLCA tissues, serum, and urine. In addition, we focus on the metabolic alterations associated with tobacco smoke and racial disparity in BLCA.

Expert commentary: Metabolomics is a powerful tool which can shed new light on BLCA development and behavior. Key metabolites may serve as possible markers of BLCA. However, prospective validation will be needed to incorporate these markers into clinical care.     

Recent insights into Mycobacterium tuberculosis through proteomics and implications for the clinic

Introduction: This review aimed at providing an update on the application of proteomics-based approaches to gain recent insights of Mycobacterium tuberculosis (M.tb) and its relevance to clinic. Proteomics and bioinformatics approaches helped in the identification and characterization of novel proteins. Studying M.tb, causative agent of tuberculosis (TB), at the proteomic level can contribute to the identification of proteins which can be considered as potential targets for developed drugs and can help us in better understanding the pathogen physiology.

Areas covered: In this review we have presented a comprehensive literature pertaining to role of proteomics in understanding M.tb. We have also focused on how the development and advancement in technology in the field of proteomics has augmented the research and played a pivotal role in answering many unexplored questions. Lastly, the application of proteomics to clinic has also been discussed.

Expert commentary: We envisage that proteomics has gained remarkable momentum over the years. Proteomics can play an important role in the discovery of biomarkers for TB and other diseases. Also, it can aid in development of effective vaccines and simple, rapid and cost-effective test for the diagnosis of TB which is crucial for the management and control of the disease.     

Sexual Differentiation of the Brain as a Manifestation of Its Plasticity

This review analyzes the published data and authors' own results on the roles of hormones and neurotransmitters in the formation of structural and functional sex-related dimorphism of the brain within the early ontogenesis period. Proof is presented in favor of the concept that classic neurotransmitters function as inductors of nerve cell differentiation in the process of individual development of the brain. Neurochemical mechanisms of the hormone–transmitter interaction in the process of sexual differentiation of the brain within pre- and/or post-natal periods are considered.     

Regulatory Properties of Adenylyl Cyclase Isoforms

Various aspects of mechanisms of the adenylyl cyclase (AC)* activity regulation are considered in the review. Variants of modulation of various AC isoform activity by G-proteins (_s- and _i subunits, -dimer), Ca²⁺-calmodulin, phosphorylation by PKA, PKC or Ca²⁺-CM-activated kinases are presented. Evidence is presented that AC functions as a signaling integrator in the cell by providing propagation and amplification of many both extracellular (with participation of hormones) and intracellular signals (interaction between Ca²⁺ and AC).