Immunoglobulin-M purification — Challenges and perspectives

Extensive research in the past two decades has led to the realization of Immunoglobulin-M (IgM) as a potential therapeutic and diagnostic agent. In order to fully exploit the potential of IgM, large quantities, in a highly pure and active form, must be available at low cost for performing clinical trials, characterization studies and quantitative-structure activity analyses. The complex physico–chemical properties, in particular its large size and labile nature renders downstream purification of IgM difficult. This review discusses the limitations and challenges associated with the current IgM purification strategies and proposes future directions for research. The uniqueness of affinity chromatography, specifically biomimetic affinity chromatography for protein purification is highlighted and its potential for IgM purification is discussed.     

River restoration concepts — goals and perspectives

An analysis of restoration projects carried out both in Austria and abroad shows that most projects are limited to design measures within the river bed with the general intention to increase habitat diversity. The various measures are not based on the type-specific characteristics of the river and thus there is a danger of creating uniform restoration stretches, independent of the specific landscape area, river morphology, discharge regime or site specific biocoenoses. Such proceeding lacks in considering a comprehensive improvement of ecological functioning of the whole river-system. To meet those demands a type-specific guiding view (Leitbild) has to be developed based on the pristine river conditions.The comparison of the river pattern including the characteristic features of its unmodified state with the actual situation leads to a comprehensive set of measures. The essential goals of such management-concepts are the integrity of the river habitat, self-regulation and self-regeneration, the preservation of intact resources, as well as the possibility to experience the uniqueness, diversity and beauty of natural river landscapes.     

Disialogangliosides and Their Interaction with Cholera Toxin—Investigation by Molecular Modeling,Molecular Mechanics and Molecular Dynamics

Abstract

Molecular mechanics and molecular dynamics studies are performed to investigate the conformational preference of cell surface disialogangliosides (GD1A, GD1B and GD3) in aqueous environment. The molecular mechanics calculation reveals that water mediated hydrogen bonding network plays a significant role in the structural stabilization of GD1A, GD1B and GD3. These water mediated hydrogen bonds not only exist between neighboring residues but also exist between residues that are separated by 2 to 3 residues in between. The conformational energy difference between different conformational states of gangliosides correlates very well with the number of water mediated and direct hydrogen bonds. The spatial flexibility of NeuNAc of gangliosides at the binding site of cholera toxin is worked out. The NeuNAc has a limited allowed eulerian space at the binding site of Cholera Toxin (2.4%). The molecular modeling, molecular mechanics and molecular dynamics of disialo- ganglioside-cholera toxin complex reveal that cholera toxin can accommodate the disialo- ganglioside GD1A in three different modes. A single mode of binding is permissible for GD1B and GD3. Direct and water mediated hydrogen bonding interactions stabilizes these binding modes and play an essential role in defining the order of specificity for different disialogangliosides towards cholera toxin. This study not only provides models for the disialoganglioside-cholera toxin complexes but also identifies the NeuNAc binding site as a site for design of inhibitors that can restrict the pathogenic activity of cholera toxin.     

Monosialogangliosides and Their Interaction with Cholera Toxin—Investigation by Molecular Modeling and Molecular Mechanics

Abstract

Molecular mechanics and molecular dynamics studies are performed to investigate the conformational preference of cell surface monosialogangliosides (GM3, GM2 and GM1) in aqueous environment. Water mediated hydrogen bonding network plays a significant role in the structural stabilization of GM3, GM2 and GM1. The spatial flexibility of NeuNAc of gangliosides at the binding site of cholera toxin reveals a limited allowed eulerian space of 2.4% with a much less allowed eulerian space (1.4%) for external galactose of GM1. The molecular mechanics of monosialoganglioside-cholera toxin complex reveals that cholera toxin can accommodate the monosialogangliosides in three different modes. Direct and water mediated hydrogen bonding interactions stabilize these binding modes and play an essential role in defining the order of specificity for different monosialogangliosides towards cholera toxin. This study identifies the NeuNAc binding site as a site for design of inhibitors that can restrict the pathogenic activity of cholera toxin.     

Conformations of Higher Gangliosides and Their Binding with Cholera Toxin—Investigation by Molecular Modeling,Molecular Mechanics,and Molecular Dynamics

Abstract

Molecular mechanics and molecular dynamics studies are performed to investigate the conformational preference of cell surface higher gangliosides (GT1A and GT1B) and their interaction with Cholera Toxin. The water mediated hydrogen bonding network exists between sugar residues in gangliosides. An integrated molecular modeling, molecular mechanics, and molecular dynamics calculation of cholera toxin complexed with GT1A and GT1B reveal that, the active site of cholera toxin can accommodate these higher gangliosides. Direct and water mediated hydrogen bonding interactions stabilize these binding modes and play an essential role in defining the order of specificity for different higher ganglioside towards cholera toxin. This study identifies that the binding site of cholera toxin is shallow and can accommodate a maximum of two NeuNAc residues. The NeuNAc binding site of cholera toxin may be crucial for the design of inhibitors that can prevent the infection of cholera.     

NCL diseases — clinical perspectives

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders and together are the most common degenerative brain diseases in childhood. They are a group of disorders linked by the characteristic accumulation of abnormal storage material in neurons and other cell types, and a degenerative disease course. All NCLs are characterized by a combination of dementia, epilepsy, and motor decline. For most childhood NCLs, a progressive visual failure is also a core feature. The characteristics of these symptoms can vary and the age at disease onset ranges from birth to young adulthood. Genetic heterogeneity, with fourteen identified NCL genes and wide phenotypic variability render diagnosis difficult. A new NCL classification system based on the affected gene and the age at disease onset allows a precise and practical delineation of an individual patient's NCL type. A diagnostic algorithm to identify each NCL form is presented here. Precise NCL diagnosis is essential not only for genetic counseling, but also for the optimal delivery of care and information sharing with the family and other caregivers. These aspects are challenging because there are also potential long term complications which are specific to NCL type. Therefore care supported by a specifically experienced team of clinicians is recommended. As the underlying pathophysiological mechanism is still unclear for all NCL forms, the development of curative therapies remains difficult. This article is part of a Special Issue entitled: The neuronal ceroid lipofuscinoses or Batten Disease.     

Biohydrogen production from microalgae—Major bottlenecks and future research perspectives

The imprudent use of fossil fuels has resulted in high greenhouse gas (GHG) emissions, leading to climate change and global warming. Reduction in GHG emissions and energy insecurity imposed by the depleting fossil fuel reserves led to the search for alternative sustainable fuels. Hydrogen is a potential alternative energy carrier and is of particular interest because hydrogen combustion releases only water. Hydrogen is also an important industrial feedstock. As an alternative energy carrier, hydrogen can be used in fuel cells for power generation. Current hydrogen production mainly relies on fossil fuels and is usually energy and CO₂-emission intensive, thus the use of fossil fuel-derived hydrogen as a carbon-free fuel source is fallacious. Biohydrogen production can be achieved via microbial methods, and the use of microalgae for hydrogen production is outstanding due to the carbon mitigating effects and the utilization of solar energy as an energy source by microalgae. This review provides comprehensive information on the mechanisms of hydrogen production by microalgae and the enzymes involved. The major challenges in the commercialization of microalgae-based photobiological hydrogen production are critically analyzed and future research perspectives are discussed. Life cycle analysis and economic assessment of hydrogen production by microalgae are also presented.     

Entomological Research： Progress and Prospects

Because of their economic importance, ancient evolutionary history, and extensive diversity, insects are of great interest to humans. As a result of their economic importance and scientific values, entomology, a branch of science that deals with insects in various aspects, has been advancing rapidly, especially in the past two decades. Coincidentally during the same period, numerous young Chinese scientists have been abroad to pursue advanced studies as graduates or to conduct research as scholars in various entomological fields. Most of them have made great achievements in their areas due to their strong commitment and diligent work. This can be evidenced by a huge number of their publications in highly ranked scientific journals. As a result of their outstanding contributions, many of them have been promoted to faculty positions in universities, government agencies, and other institutions around the world. Armed with rich research experience, modern technologies, and comprehensive expertise, these overseas entomologists want to make contributions to accelerate entomological research in China. The book Entomological Research： Progress and Prospects is one of their strides in this direction.     

Molecular genetics of preeclampsia and HELLP syndrome — A review

Preeclampsia is characterised by new onset hypertension and proteinuria and is a major obstetrical problem for both mother and foetus. Haemolysis elevated liver enzymes and low platelets (HELLP) syndrome is an obstetrical emergency and most cases occur in the presence of preeclampsia. Preeclampsia and HELLP are complicated syndromes with a wide variety in severity of clinical symptoms and gestational age at onset. The pathophysiology depends not only on periconceptional conditions and the foetal and placental genotype, but also on the capability of the maternal system to deal with pregnancy. Genetically, preeclampsia is a complex disorder and despite numerous efforts no clear mode of inheritance has been established. A minor fraction of HELLP cases is caused by foetal homozygous LCHAD deficiency, but for most cases the genetic background has not been elucidated yet. At least 178 genes have been described in relation to preeclampsia or HELLP syndrome. Confined placental mosaicism (CPM) is documented to cause early onset preeclampsia in some cases; the overall contribution of CPM to the occurrence of preeclampsia has not been adequately investigated yet. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.