Evo-Devo of the Human Vertebral Column: On Homeotic Transformations, Pathologies and Prenatal Selection

Homeotic transformations of vertebrae are particularly common in humans and tend to come associated with malformations in a wide variety of organ systems. In a dataset of 1,389 deceased human foetuses and infants a majority had cervical ribs and approximately half of these individuals also had missing twelfth ribs or lumbar ribs. In?~10?% of all cases there was an additional shift of the lumbo-sacral boundary and, hence, homeotic transformations resulted in shifts of at least three vertebral boundaries. We found a strong coupling between the abnormality of the vertebral patterns and the amount and strength of associated malformations, i.e., the longer the disturbance of the vertebral patterning has lasted, the more associated malformations have developed and the more organ systems are affected. The germ layer of origin of the malformations was not significantly associated with the frequency of vertebral patterns. In contrast, we find significant associations with the different developmental mechanisms that are involved in the causation of the malformations, that is, segmentation, neural crest development, left-right patterning, etc. Our results, thus, suggest that locally perceived developmental signals are more important for the developmental outcome than the origin of the cells. The low robustness of vertebral A-P patterning apparent from the large number of homeotic transformations is probably caused by the strong interactivity of developmental processes and the low redundancy of involved morphogens during early organogenesis. Additionally, the early irreversibility of the specification of the A-P identity of vertebrae probably adds to the vulnerability of the process by limiting the possibility for recovery from developmental disturbances. The low developmental robustness of vertebral A-P patterning contrasts with a high robustness of the A-P patterning of the vertebral regions. Not only the order is invariable, also the variation in the number of vertebrae per region is small. This robustness is in agreement with the evolutionary stability of vertebral regions in tetrapods. Finally, we propose a new hypothesis regarding the constancy of the presacral number of vertebrae in mammals.     

Neuroregenerative strategies in the brain: emerging significance of bone morphogenetic protein 7 (BMP7)

Every year thousands of people suffer from brain injuries and stroke, and develop motor, sensory, and cognitive problems as a result of neuronal loss in the brain. Unfortunately, the damaged brain has a limited ability to enact repair and current modes of treatment are not sufficient to offset the damage. An extensive list of growth factors, neurotrophic factors, cytokines, and drugs has been explored as potential therapies. However, only a limited number of them may actually have the potential to effectively offset the brain injury or stroke-related problems. One of the treatments considered for future brain repair is bone morphogenetic protein 7 (BMP7), a factor currently used in patients to treat non-neurological diseases. The clinical application of BMP7 is based on its neuroprotective role in stroke animal models. This paper reviews the current approaches considered for brain repair and discusses the novel convergent strategies by which BMP7 potentially can induce neuroregeneration.     

Life at elevated CO2 modifies the cell composition of Chromera velia (Chromerida)

We investigated the response to high CO₂ of Chromera velia, a photosynthetic relative of apicomplexan parasites that is possibly involved in symbiotic associations with scleractinian corals. The inorganic C content in the proximity of the symbiotic algal cells within the tissues of scleractinians is disputed. According to some authors, it is very high. A higher C content in the endodermal tissues of scleractinians than in the external environment may have favoured the constitution of symbiosis with organisms such as Symbiodinium and Chromera that have a type II Rubisco, which is intrinsically ill suited to low CO₂ environments. We thus cultured C. velia at the very high inorganic C estimated by some authors and assessed its growth and photosynthetic performance. We also evaluated whether these conditions affected C allocation and elemental stoichiometry in C. velia cells by state-of-the-art Fourier transform infrared spectroscopy and total reflection X-ray fluorescence spectrometry in combination with more traditional biochemical and physiological techniques. Our results demonstrated that C. velia was capable of coping with very high CO₂, which even stimulated biomass production and increased N, P, Mn, Fe and Zn use efficiency. Growth at elevated CO₂ changed the stoichiometric relationships among elements in C. velia cells, but had no effect on the relative abundance of the main organic pools. The high CO₂ in the animal tissue surrounding the photosynthetic cells may therefore facilitate C. velia life in symbiosis.     

Deletion of Irs2 causes reduced kidney size in mice: role for inhibition of GSK3β?

Background  

Male Irs2 ^-/- mice develop fatal type 2 diabetes at 13-14 weeks. Defects in neuronal proliferation, pituitary development and photoreceptor cell survival manifest in Irs2 ^-/- mice. We identify retarded renal growth in male and female Irs2 ^-/- mice, independent of diabetes.     

Study on the reaction of 2,3-dihydroxybenzoic acid with molybdenum in aqueous solution. I. Synthesis and characterization of the oligomeric complexes formed

Dimeric or oligomeric oxo-complexes of Mo(VI) with 2,3-dihydroxybenzoic acid were prepared in aqueous solutions in the presence or not of K₂S₂O₅ (acting as a reducing agent) in various conditions. The complexes were found to contain the cis-(Mo₂O₅)²⁺ core and the ligands in the catecholate, semiquinonate or mixed valence oxidation form, depending on the reaction conditions and especially on the presence or not of the reductant. The isolated complexes in the presence or absence of reductant and the oxidation products in solution in the presence of air were studied via elemental, thermogravimetric and electrochemical analysis, Infrared, Raman, NMR and ESR spectroscopies and Electrospray Mass Spectra. The general molecular formula for the complexes is {[(PPh₄)₂(Mo₂O₅L₂X₂] · xH₂O)}_n, where the coordinated ligand’s L oxidation form varies and X involves coordinated water or hydroxyl group depending on the ligand oxidation state.     

Glycation of lysine-containing dipeptides.

Protein glycation through Maillard reaction (MR) is a fundamental reaction both in foods and in the human body. The first step of the reaction is the formation of Amadori product (AP) that is converted into intermediate and advanced MR products during reaction development. Although the MR is not an enzymatic reaction, a certain degree of specificity in the glycation site has been observed. In the present study, we have monitored the glycation of different lysine-containing dipeptides to evaluate the influence on the NH(2) reactivity of the neighboring amino acid.Lysine dipeptides were reacted with glucose, galactose, lactose and maltose. The formation and identification of glycated compounds were monitored by mass spectrometry (MALDI-TOF and ESI-MS/MS) and by HPLC of their Fmoc derivatives. MS/MS analysis showed that the glucose APs formed on dipeptides have a characteristic fragmentation pattern: the fragment at [M - 84](+) due to the formation of pyrylium and furylium ion is mainly present in the monoglucosylated form, while the [M - 162](+) and the [M - 324](+) are more evident in the fragmentation pattern of the diglucosylated forms.The nature of the vicinal amino acids strongly affects lysine reactivity towards the different carbohydrates: the presence of hydrophobic residues such as Ile, Leu, Phe strongly increases lysine reactivity. Contrasting results were obtained with basic residues. The Lys-Arg dipeptide was among the most reactive while the Lys-Lys was not.     

BATS: a Bayesian user-friendly software for Analyzing Time Series microarray experiments

Background  

Gene expression levels in a given cell can be influenced by different factors, namely pharmacological or medical treatments. The response to a given stimulus is usually different for different genes and may depend on time. One of the goals of modern molecular biology is the high-throughput identification of genes associated with a particular treatment or a biological process of interest. From methodological and computational point of view, analyzing high-dimensional time course microarray data requires very specific set of tools which are usually not included in standard software packages. Recently, the authors of this paper developed a fully Bayesian approach which allows one to identify differentially expressed genes in a 'one-sample' time-course microarray experiment, to rank them and to estimate their expression profiles. The method is based on explicit expressions for calculations and, hence, very computationally efficient.