Emergence and the human genome

Peer reviewedThe (human) genome functions as an open system within human nutritional, economic, cultural, intellectual and emotional contexts. Of profound importance is the extent of free will that emerged with our cognitive and consciousness traits. We have been instrumental in creating particular environments and semiotics according to which we live and with which our genes are expressed. The possibility exists that an information continuum between genes, brain and environment may follow quantum rules and exhibit correlated properties that result in coordinated behaviour (entanglement), even without signal transfer or interaction. With the unprecedented technological advances made during the last century, for the first time a biological organism can, in theory, purposefully design its own future evolution. This is likely to remain limited by ultimate unpredictability due to emergent novelties arising during the process. The effect(s) of a strong human strategic guiding influence, however, implies a tremendous moral responsibility to help shape future outcomes which will enhance the continued existence of quality Life on Earth. How are we doing so far, and how can we exploit knowledge of the possible structural basis of genomic memory and the principles linked with self organisation and emergence to avoid recurrence of outcomes previously shown to have had negative consequences for Life. Can we feed back crucial brain memories to the germline contrary to prevailing dogma, and does this contribute to a compound interest situation not only of intellectual ability but also of a hereditary basis for augmenting ("negative", Machiavellian type) moral behaviour previously found to be successful for pure biological survival?Research Institute for Theology and Religio

Profound Morphological Changes in the Erythrocytes and Fibrin Networks of Patients with Hemochromatosis or with Hyperferritinemia, and Their Normalization by Iron Chelators and Other Agents

It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs) may play an important role during thrombotic events. Therefore the purpose of the current study was to assess whether RBCs had an altered morphology in individuals with hereditary hemochromatosis (HH), as well as some who displayed hyperferritinemia (HF). Using scanning electron microscopy, we also assessed means by which the RBC and fibrin morphology might be normalized. An important objective was to test the hypothesis that the altered RBC morphology was due to the presence of excess unliganded iron by removing it through chelation. Very striking differences were observed, in that the erythrocytes from HH and HF individuals were distorted and had a much greater axial ratio compared to that accompanying the discoid appearance seen in the normal samples. The response to thrombin, and the appearance of a platelet-rich plasma smear, were also markedly different. These differences could largely be reversed by the iron chelator desferal and to some degree by the iron chelator clioquinol, or by the free radical trapping agents salicylate or selenite (that may themselves also be iron chelators). These findings are consistent with the view that the aberrant morphology of the HH and HF erythrocytes is caused, at least in part, by unliganded (‘free’) iron, whether derived directly via raised ferritin levels or otherwise, and that lowering it or affecting the consequences of its action may be of therapeutic benefit. The findings also bear on the question of the extent to which accepting blood donations from HH individuals may be desirable or otherwise

Mineralisation of soft and hard tissues and the stability of biofluids

Evidence is provided from studies on natural and artificial biofluids that the sequestration of amorphous calcium phosphate by peptides or proteins to form nanocluster complexes is of general importance in the control of physiological calcification. A naturally occurring mixture of osteopontin peptides was shown, by light and neutron scattering, to form calcium phosphate nanoclusters with a core–shell structure. In blood serum and stimulated saliva, an invariant calcium phosphate ion activity product was found which corresponds closely in form and magnitude to the ion activity product observed in solutions of these osteopontin nanoclusters. This suggests that types of nanocluster complexes are present in these biofluids as well as in milk. Precipitation of amorphous calcium phosphate from artificial blood serum, urine and saliva was determined as a function of pH and the concentration of osteopontin or casein phosphopeptides. The position of the boundary between stability and precipitation was found to agree quantitatively with the theory of nanocluster formation. Artificial biofluids were prepared that closely matched their natural counterparts in calcium and phosphate concentrations, pH, saturation, ionic strength and osmolality. Such fluids, stabilised by a low concentration of sequestering phosphopeptides, were found to be highly stable and may have a number of beneficial applications in medicine

Nucleus-targeted Dmp1 transgene fails to rescue dental defects in Dmp1 null mice

Dentin matrix protein 1 (DMP1) is essential to odontogenesis. Its mutations in human subjects lead to dental problems such as dental deformities, hypomineralization and periodontal impairment. Primarily, DMP1 is considered as an extracellular matrix protein that promotes hydroxyapatite formation and activates intracellular signaling pathway via interacting with αvβ3 integrin. Recent in vitro studies suggested that DMP1 might also act as a transcription factor. In this study, we examined whether full-length DMP1 could function as a transcription factor in the nucleus and regulate odontogenesis in vivo. We first demonstrated that a patient with the DMP1 M1V mutation, which presumably causes a loss of the secretory DMP1 but does not affect the nuclear translocation of DMP1, shows a typical rachitic tooth defect. Furthermore, we generated transgenic mice expressing (NLS)DMP1, in which the endoplasmic reticulum (ER) entry signal sequence of DMP1 was replaced by a nuclear localization signal (NLS) sequence, under the control of a 3.6 kb rat type I collagen promoter plus a 1.6 kb intron 1. We then crossbred the (NLS)DMP1 transgenic mice with Dmp1 null mice to express the (NLS)DMP1 in Dmp1-deficient genetic background. Although immunohistochemistry demonstrated that (NLS)DMP1 was localized in the nuclei of the preodontoblasts and odontoblasts, the histological, morphological and biochemical analyses showed that it failed to rescue the dental and periodontal defects as well as the delayed tooth eruption in Dmp1 null mice. These data suggest that the full-length DMP1 plays no apparent role in the nucleus during odontogenesis

HH and wild type individuals with age, gender, free iron, transferrin and % saturation levels.

<p>HH and wild type individuals with serum ferritin (normal values: females ≤200 ng/mL⁻¹; males ≤300 ng/mL⁻¹) gender, age, serum iron (normal values: 11.6 – 31.4 µmol/L⁻¹), transferrin (normal values: 2.2 – 3.7 g/L⁻¹) and % saturation levels (normal values: 20 – 50%). Bold values indicate where levels do not fall into normal value.</p

Micrographs of samples from patients with hereditary hemochromatosis with added clioquinol.

<p><b>A</b>) Whole blood with added 10 mM clioquinol (H63D/wild type); <b>B</b>) Whole blood, with added thrombin and 10 mM clioquinol (H63D/wild type); <b>C</b>) Platelet rich plasma smear, with added thrombin and 10 mM clioquinol (H63D/wild type); <b>D</b>) Whole blood with added 0.5 mM clioquinol; <b>E</b>) Whole blood, with added thrombin and 0.5 mM clioquinol (H63D/wild type); <b>F</b>) Platelet rich plasma smear, with added thrombin and 0.5 mM clioquinol (H63D/wild type); <b>G</b>) Light microscopy of whole blood with 0.5 mM clioquinol (C282Y/wild type). All SEM micrographs scales  = 1 µm; light microscopy micrograph scale  = 10 µm.</p