DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis

Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.     

Asexual reproduction: Genetics and evolutionary aspects

Reproduction is essential to all organisms if they are to contribute to the next generation. There are various means and ways of achieving this goal. This review focuses on the role of asexual reproduction for eukaryotic organisms and how its integration in a life cycle can influence their population genetics and evolution. An important question for evolutionary biologists as to why some organisms reproduce sexually, as opposed to asexually, is addressed. We also discuss the economic and medical importance of asexual organisms. Received 4 December 2006; received after revision 25 January 2007; accepted 20 February 2007     

Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion

Mitochondrial DNA (mtDNA) depletion syndrome (MDS; MIM 251880) is a prevalent cause of oxidative phosphorylation disorders characterized by a reduction in mtDNA copy number. The hitherto recognized disease mechanisms alter either mtDNA replication (POLG (ref. 1)) or the salvage pathway of mitochondrial deoxyribonucleosides 5'-triphosphates (dNTPs) for mtDNA synthesis (DGUOK (ref. 2), TK2 (ref. 3) and SUCLA2 (ref. 4)). A last gene, MPV17 (ref. 5), has no known function. Yet the majority of cases remain unexplained. Studying seven cases of profound mtDNA depletion (1-2% residual mtDNA in muscle) in four unrelated families, we have found nonsense, missense and splice-site mutations and in-frame deletions of the RRM2B gene, encoding the cytosolic p53-inducible ribonucleotide reductase small subunit. Accordingly, severe mtDNA depletion was found in various tissues of the Rrm2b-/- mouse. The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis.     

Anti-bovine beta-lactoglobulin antibodies react with a human lactoferrin fragment and bovine beta-lactoglobulin present in human milk

Human milk samples react against anti-bovine beta-lactoglobulin rabbit antibodies, as measured by a competitive radioimmunoassay. Immunoreactivity was positive even in milk from mothers consuming a diet free of cow's milk. An increase with a diet rich in cow's milk proteins was detected by immunoelectrophoresis. The human milk fraction cross-reacting with anti-bovine beta-lactoglobulin antibodies corresponds to the 20 kDa fragment from the N-terminal end of human lactoferrin. Three regions of this fragment exhibit sequence homology with a sequence contained in cow's beta-lactoglobulin (between residues 124 and 141).     

Aristotelism of Difference

There is a central doctrine in Aristotle that usually isn’t recognized in its importance: the affirmation of the difference and the plurality. In the course of the centuries, Aristotelism lost which was perhaps its most characteristic and specific feature versus Platonism, that is, its criticism of unity and its defense of plurality. The first principle is not the One but the plurality. The horizon of thinking is not the unity but the diversity of the logos. The unity of the logos presupposes the differences within reality. Heidegger attracted attention to the peculiarity of the practical philosophy of Aristotle. It was the case of dialectics, rhetoric, poetics, ethics, politics, etc. We are referring to knowledges that are art rather than science. Nothing is so differentiated as human action, as it is always performed from a new starting point. Dialectic and rhetorical speeches are always circumscribed to the individual.     

Operational and Strategic Decisions in Hospitality. Lessons from an Action Research Process

Systemic Practice and Action Research - The aim of this article is to find measures that reduce personnel costs in a catering company through the optimization of routes and tasks for staff to...     

A Brief Crack of Light?

This is a contribution to an inquiry into the historical meaning of Professor Checkland's soft systems thinking. Heidegger's picture of the present postmodern (or high-modern) epoch provides a context for unfolding that historical meaning. The discussion is focused on the possibility that Checkland's thinking could represent one of the "brief cracks" in the solid neo-instrumental way of appearing (whatever-is-the-case) that characterizes our present epoch.     

Molecular recycling within amyloid fibrils

Amyloid fibrils are thread-like protein aggregates with a core region formed from repetitive arrays of beta-sheets oriented parallel to the fibril axis. Such structures were first recognized in clinical disorders, but more recently have also been linked to a variety of non-pathogenic phenomena ranging from the transfer of genetic information to synaptic changes associated with memory. The observation that many proteins can convert into similar structures in vitro has suggested that this ability is a generic feature of polypeptide chains. Here we have probed the nature of the amyloid structure by monitoring hydrogen/deuterium exchange in fibrils formed from an SH3 domain using a combination of nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The results reveal that under the conditions used in this study, exchange is dominated by a mechanism of dissociation and re-association that results in the recycling of molecules within the fibril population. This insight into the dynamic nature of amyloid fibrils, and the ability to determine the parameters that define this behaviour, have important implications for the design of therapeutic strategies directed against amyloid disease.