Aspects on properties, use and ethical considerations of embryonic stem cells – A short review

Mammalian embryonic stem cells have the potential to differentiate into all cell types of an adult individual. The culturing of human embryonic stem cells renders possible studies that were previously only available in animal models. Embryonic stem cells constitute a particularly attractive tool for studies of self-renewal, commitment, differentiation, maturation and cell-cell interaction. There is currently considerable hope that studies of embryonic stem cells will lead to new therapies; either by themselves, through cell replacement strategies, or by generating results assisting other fields of research to reach clinical results. There are, however, considerable challenges to be met before embryonic stem cells can be used in large-scale clinical trials.Stem cell research is an area that has given rise to much debate internationally, within science, law and politics as well as within philosophy and ethics. The ethical attitudes expressed in the public debate over stem cell research notably divide over three important distinctions: (1) Reproductive versus therapeutic cloning; (2) Using already existing embryos versus producing new embryos for research purposes; (3) Production of embryos from eggs and sperm versus through somatic-cell nuclear transfer. The potential medical benefits that may result from embryonic stem cell research arguably support a continued development in this area. However, some opponents argue that this research offends the (relative or absolute) moral status of an unborn human. Furthermore, the research would probably prove to be a both time-consuming and very expensive method for treating disease. Thus, the questions arise whom the new technique wouldbenefit and at what cost, if ever developed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen

Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterised by profound congenital sensorineural deafness and prolongation of the QT interval on the electrocardiogram, representing abnormal ventricular repolarisation. In a study of ten British and Norwegian families with JLNS, we have identified all of the mutations in the KCNQ1 gene, including two that are novel. Of the nine mutations identified in this group of 10 families, five are nonsense or frameshift mutations. Truncation of the protein proximal to the recently identified C-terminal assembly domain is expected to preclude assembly of KCNQ1 monomers into tetramers and explains the recessive inheritance of JLNS. However, study of a frameshift mutation, with a dominant effect phenotypically, suggests the presence of another assembly domain nearer to the N-terminus.     

Effect of extrusion on trypsin inhibitor activity and nutrient digestibility of diets based on fish meal, soybean meal and white flakes

The effects of moist extrusion processing of diets containing fish meal (FM) and conventional defatted soybean meal (SBM) or untoasted defatted soybean meal (white flakes [WF]) on amino acid composition, trypsin inhibitor activity (TIA), and apparent total tract digestibility of nutrients were studied. Three diets with the nutritional characteristics of feeds for salmonid fish were formulated: one control based on FM as protein source and two others where 40% of total amino acids from FM were substituted by either SBM or WF. Each diet was fed to mink either as an unextruded mixture of the ingredients or as extruded pellets in order to determine the effect of extrusion processing. Extrusion did not change the amino acid composition of the diets significantly, but reduced the TIA of both diets containing soy products by approximately 76%. Intake of the unextruded WF diet was only one-third compared with the other diets. The dry matter concentration in faeces from mink fed diets containing soy products was significantly lower than in mink fed the FM diet. Digestibility of crude protein, all amino acids and fat was lower, but starch higher, in the unextruded WF diet than in the FM and SBM diets, whereas no significant differences were found among the extruded diets. Extrusion of the WF diet increased digestibility of protein and all amino acids. The greatest increase in digestibility after extrusion of the WF diet was observed for cysteine followed by tryptophan. Extrusion of the FM and SBM diets had no significant effect on amino acid digestibility. Digestibility of starch was, in general, increased by extrusion. It is concluded that the heat treatment involved in typical moist extrusion processing used for fish feed may be sufficient to inactivate most of the TIA in unheated soybean meal, and to increase digestibility of the protein in WF to approximately the same level as found for SBM and FM. Still, extrusion is a lenient process with minor effects on nutrient digestibility of diets containing fish meal or toasted soybean meal as major protein sources.     

The relation of emotions to placebo responses

The hypothesis put forth is that expectations of treatment effects reduce negative emotions and thereby reduce symptoms, e.g. pain. Negative emotions increase pain, and it is hypothesized that placebos reduce pain by reducing negative emotions, i.e. feelings of nervousness, fear and anxiety. Placebo analgesia has been shown to be mediated via opioid activity, and relaxation increases opioid activity. The placebo acquires its relaxing effect due to verbal information that pain will be reduced, or due to associations between the placebo and the reduction in pain after effective treatment. Thus, the placebo signals that unpleasantness will be less after administration of the placebo. This involves negative reinforcement which is due to activation of a dopaminergic system that has been found to be activated during placebo analgesia and is involved in positive emotions. The nocebo effect of increased pain is, consistent with this model, because of increased fear and anxiety. The new aspect of the presented model is the hypothesis that expectations reduce negative emotions, and that negative reinforcement that involves the dopaminergic reinforcement system should be a contributor to placebo responses.     

Taking due care: moral obligations in dual use research

In the past decade, the perception of a bioterrorist threat has increased and created a demand on life scientists to consider the potential security implications of dual use research. This article examines a selection of proposed moral obligations for life scientists that have emerged to meet these concerns and the extent to which they can be considered reasonable. It also describes the underlying reasons for the concerns, how they are managed, and their implications for scientific values. Five criteria for what constitutes preventable harm are suggested and a number of proposed obligations for life scientists are considered against these criteria, namely, the obligations to prevent bioterrorism; to engage in response activities; to consider negative implications of research; not to publish or share sensitive information; to oversee and limit access to dangerous material; and to report activities of concern. Although bioterrorism might be perceived as an imminent threat, the analysis illustrates that this is beyond the responsibility of life scientists either to prevent or to respond to. Among the more reasonable obligations are duties to consider potential negative implications of one's research, protect access to sensitive material, technology and knowledge, and report activities of concern. Responsibility, therefore, includes obligations concerned with preventing foreseeable and highly probable harm. A central conclusion is that several of the proposed obligations are reasonable, although not unconditionally.     

EXTRACELLULAR POLYSACCHARIDES FROM ANKISTRODESMUS DENSUS (CHLOROPHYCEAE)

The dissolved extracellular compounds produced by the Chlorococcalean Ankistrodesmus densus Kors. were investigated for their molecular masses and chemical composition. Gel permeation chromatography showed apparent relative molecular masses of 2 × 10⁶ and 10⁴, respectively, for two distinct fractions, termed A and B. The higher molecular weight fraction (A) contained mainly fucose and 3- O -methylgalactose, whereas galactose, glucose, mannose, and rhamnose were present in smaller amounts. Methylation analyses showed that the main structural features are fucose as a highly branched part of polymer A with substitutions in both position 2 and position 4, the substitutions on one of those positions being primarily terminal 3- O -methylgalactose and the other one involved as the linkage of the main chain of the polymer. Because of the presence of both fucose and 3- O -methylgalactose, this polymer is highly hydrophobic. In fraction B, mannose represented more than 60% of the carbohydrate material present, whereas the remaining part contained rhamnose, fucose, xylose, and glucose in almost equal amounts. 3- O -methylgalactose and galactose were present as minor elements. Fraction B is basically a mannose-containing polymer in which the mannose units are either 1→4 or 1→2 linked. Traces of glucuronic acid and protein were present in both fractions; neither sulfate nor phosphate was detected.