Effects of citrate on the composition and enzymic coagulation of colloidal bovine casein aggregates

Colloidal casein aggregates (CCA) prepared from soluble whole bovine caseinates in the presence of Ca²⁺ and phosphate (Pi) ions by addition of different citrate (Cit) concentrations showed different mineral and proteic composition. Citrate concentration conditions the Ca and Pi concentrations incorporated into CCA, probably due to the complexing effect of this anion on calcium. A significant change in the incorporated Ca/Pi ratio at 8 mM citrate could very likely be associated to changes in CCA net charge. The incorporation of individual caseins to the colloidal particles obtained, as well as their average size and size distribution, depended also on the Cit concentration used [Cit]_P. α_S- and β-caseins assembled in the CCA structure sharply decreased at a [Cit]_P higher than 15 mM, i.e., at a low Ca²⁺ concentration in the aggregates, showing that the presence of this cation is necessary for the incorporation of these caseins. An inverse relationship between the aggregation step rate in CCA enzymic coagulation and their average size was observed. The aggregation rate vs the average size curve obtained at [Cit]_P 8 mM clearly differed from the curves obtained at 10 and 12 mM, respectively, a fact probably related to a change in the CCA net charge. This behavior showed the effect of citrate concentration on CCA functional properties.     

Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia

Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer.     

A monopole mass filter with a hyperbolic V-shaped electrode

In this article we compare the classical monopole mass filter of von Zahn and the monopole mass filter with a hyperbolic V-shaped electrode. The experimental results and those of computer simulation for both mass spectrometers are presented. We show that the replacement of a conventional 90 degrees V-shaped electrode by an electrode with a hyperbolic profile substantially improves the peak shape of any given mass, and increases the mass resolution by a factor of 3-4 and the abundance sensitivity by a factor of 100. The potential of high analytical performance combined with electroforming techniques for electrode manufacture indicate future practical uses of such instruments. Copyright 1999 John Wiley & Sons, Ltd.     

Local canted spin behaviour in Co1.4−x Zn x Ge0.4Fe1.2O4 spinels: A macroscopic, mesoscopic and microscopic study

DC magnetization, neutron depolarization and neutron diffraction (with both polarized and unpolarized neutrons) measurements have been reported for the Co_1.1−x Zn _x Ge_0.1Fe_1.2O₁ spinels with x=0.5, 0.6 and 0.7. Neutron depolarization and neutron diffraction measurements confirm the presence of a long range ferrimagnetic ordering of the local canted spins in these ferrite samples. The observed features of low field magnetization have been explained under the framework of thermally activated domain wall movement of ferrimagnetic arrangement of local canted spins. An important role of magnetic anisotropy (due to the presence of Co²⁺ ions) in establishing the magnetic ordering and domain kinetics in these ferrites has been observed.     

Determination of electron affinity of carbonyl radicals by means of negative ion mass spectrometry

Appearance energies of [M-H](-) ions from carbonyl compounds R-CO-R' (R,R' = H, CH(3), NH(2), OH) have been measured by means of negative ion mass spectrometry in resonant electron capture mode. Values of electron affinity of the corresponding radicals, CH(2)&dbond;C(X)O, NH&dbond;C(X)O and O&dbond;C(X)O, have been determined. Copyright 1999 John Wiley & Sons, Ltd.     

Moving towards individualized medicine with pharmacogenomics

Individuals respond differently to drugs and sometimes the effects are unpredictable. Differences in DNA that alter the expression or function of proteins that are targeted by drugs can contribute significantly to variation in the responses of individuals. Many of the genes examined in early studies were linked to highly penetrant, single-gene traits, but future advances hinge on the more difficult challenge of elucidating multi-gene determinants of drug response. This intersection of genomics and medicine has the potential to yield a new set of molecular diagnostic tools that can be used to individualize and optimize drug therapy.