PubMed Health⌕ Search

Biomedical subjects

K Mortensen

Publications and source records attributed to K Mortensen.

At least 55 records · Page 3Linked to original sources
PubMed1994

The growth of fractal humic acids: cluster correlation and gel formation.

The growth of humic acids, prepared by a gentle method from two different kinds of soils (I and II), has been studied using small-angle neutron scattering at an acidity corresponding to pH 5.0 and 0.10 M ionic strength (NaCl). Humic acids aggregate either to large clusters with a fractal dimension of 2.3 and an average diameter of 1720 A (I) or to clusters with an average diameter of 700 A (II). After storage for 2 days at 4 degrees C, the latter aggregates (II) formed a gel. In a step toward gelation, we observed cluster-cluster interaction from the neutron-scattering data in the form of a correlation peak. These differences in size can be explained by assuming that the smaller particles (II) are trapped into a nonequilibrium state characterized by the temperature-solvent condition. The importance of a humic acid gel network for the conservation of water and nutrients in the environment is discussed.

Gels↗
PubMed1994

Interparticle interactions and structure in nonideal solutions of human serum albumin studied by small-angle neutron scattering and Monte Carlo simulation.

Moderately or highly concentrated nonideal solutions of macromolecules are very important systems e.g. in biology and in many technical processes. In this work we have used the small-angle neutron scattering technique (SANS) to study the interactions and interparticle structure in solutions of human serum albumin (HSA) up to a concentration of 0.26 g/cm3 in 1.08 M NaCl. In order to obtain a model for the interactions we have combined the SANS data with results obtained by Monte Carlo simulations where we calculate the structure factor S(Q) and the pair correlation function g(r). The advantage of using the Monte Carlo method is that completely general models for the particle shape and the interactions can be considered. It is found that the SANS data can be explained by a model where the shape of the HSA molecule is approximated by an ellipsoid of revolution with semiaxes a = 6.8 nm and b = c = 1.9 nm. The interaction potential between the HSA molecules consists of two parts: (a) the molecules are hard and impenetrable and (b) the molecules are surrounded by a spherically symmetric repulsive potential which can be expressed by an empirical formula containing the HSA concentration and the centre-centre distances as the only variables.

Humans↗
PubMed1992

Structure of RecA-DNA complexes studied by combination of linear dichroism and small-angle neutron scattering measurements on flow-oriented samples.

By combining anisotropy of small-angle neutron scattering (SANS) and optical anisotropy (linear dichroism, l.d.) on flow-oriented RecA-DNA complexes, the average DNA-base orientation has been determined in RecA complexes with double-stranded (ds) as well as single-stranded (ss) DNA. From the anisotropy of the two-dimensional SANS intensity representation, the second moment orientation function S is obtained. Knowledge of S is crucial for the interpretation of l.d. spectra in terms of orientation of the DNA bases and the aromatic amino acid residues. The DNA-base planes are essentially perpendicular to the fibre axis of the complex between RecA and dsDNA in the presence of cofactor ATP gamma S. A somewhat tilted base geometry is found for the RecA-ATP gamma S complexes with single-stranded poly(dT) and poly(d epsilon A). This behaviour contrasts the RecA-ssDNA complex formed without cofactor which displays a poor orientation of the bases. Well-ordered bases in the ssDNA-RecA complex is possibly reflecting the role of RecA in preparing a nucleotide strand for base-pairing in the search-for-homology process. While the central SANS intensity is essentially independent of the pitch of the helical complex, a secondary intensity maximum, which becomes focused upon flow orientation, is found to be a sensitive measure of the pitch. The pitch values for the complexes compare well with cryo-electron microscopy results but are slightly larger than those seen for uranyl-stained samples.

Adenosine Triphosphate↗
PubMed1992

Temperature dependence of the kinetics of the urea-induced dissociation of human plasma alpha 2-macroglobulin into half-molecules. A minimum rate at 15 degrees C indicates hydrophobic interaction between the subunits.

The kinetics of the urea-induced dissociation of human plasma alpha 2-macroglobulin to half-molecules has been studied as a function of temperature by using small-angle scattering of X-rays and neutrons. The most striking result of the present investigation is that there is a minimum in reaction rate at about 15 degrees C, and that the rate increases when the temperature is lowered, or raised, from that value. By analyzing the first-order rate constants in terms of transition-state theory it was found that the dissociation is associated with a large and positive change in heat capacity between the activated complex and native alpha 2-macroglobulin (delta CP is in the range 5 to 6 kJ mol-1 K-1). In analogy with pure thermodynamic investigations, where a large change in heat capacity normally is interpreted as a melting of hydrophobic interaction, we therefore propose that hydrophobic interaction is involved in the so-called non-covalent interactions between the subunits of alpha 2-macroglobulin. As a result of the present investigation, it also follows that the free energy of activation delta G has a maximum at about 32 degrees C, whereas the enthalpy of activation delta H and the entropy of activation delta S are zero at about 15 degrees C and 32 degrees C, respectively. These temperatures are slightly dependent upon the concentration of urea and upon whether the reaction is run in a 1H or a 2H medium. Furthermore, from the kinetic point of view, at low temperature the reaction can be characterized as enthalpy driven, whereas at high temperature, it can be characterized as entropy driven.

Humans↗
PubMed1992

Contrast variation studies of clathrin coated vesicles by small-angle neutron scattering.

Structural information on clathrin coated vesicles has been obtained by small angle neutron scattering using contrast variation. A characteristic peak in the neutron scattering profile, which is apparent in 75% D2O, as well as in H2O, disappears when contrast matching the protein component of the coated vesicles in 42% D2O. Neutron, as well as dynamic, light scattering give a coated vesicle size of about 900 A in H2O and D2O, but for neutron scattering the diameter decreases when matching out the protein coat of the clathrin coated vesicles. From the match point for the clathrin coated vesicles it is demonstrated that the clathrin cages do contain internal membrane. The mass of 34 MD and composition of 75% protein and 25% lipid found from the analysis of the small-angle scattering data are both in good agreement with the values reported in the literature. Electron microscopy gives an average outer diameter of 880 A for the coated vesicles and an average diameter of 460 A for the vesicle itself.

Biophysical Phenomena↗
PubMed1992

Increasing incidence of early onset type 1 (insulin-dependent) diabetes mellitus: a study of Danish male birth cohorts.

To provide information of the incidence trends of Type 1 (insulin-dependent) diabetes mellitus we performed a cohort study of a series of Danish male birth cohorts. All male livebirths in Denmark between 1 January 1949 and 31 December 1964, were investigated regarding the development of Type 1 diabetes during the first 20 years of life using the files of the Danish Conscript Board, supplemented by a search in the Danish National Registry of Deaths. Diagnosis was verified and clinical information obtained from medical records. The material is estimated to be more than 95% complete. A total of 1705 diabetic subjects were identified of whom 23 were not representative of idiopathic Type 1 diabetes. The cumulative rate of Type 1 diabetes development during the first 20 years of life increased from 2.37 to 2.90 per 1000 for the first eight and last eight birth cohorts, respectively. A log-linear analysis of the incidence revealed significantly increasing incidence rates, independent of age effects, with a maximum in the late 1970's. About 75% of the cases presented short duration of symptoms prior to diagnosis, and only very few cases were diagnosed incidentally. Cases were diagnosed relatively less frequently during summer months than during winter months.

Adolescent↗
PubMed1992

Breast feeding and the development of type 1 diabetes mellitus.

A case-control study was conducted to study the proposed inverse relationship between breast feeding and incidence of Type 1 diabetes mellitus. All Danish diabetic men born in Copenhagen during 1959-1964 and/or residing there for the first year of life (n = 119) were identified and a search made for their post-natal health visitor records. These include data on birth weight, birth length, immunizations, and feeding habits. A total of 77 cases were re-identified. No differences were found with respect to clinical characteristics between these cases and those not identified. For each diabetic subject, two control children with date of birth identical to the diabetic cases were drawn from health visitor records. Cases and controls did not differ with respect to maternal age, or birth weight or length. Overall, the statistical analysis failed to confirm the hypothesis of an association between duration of breast feeding and subsequent diabetes risk.

Adult↗
PubMed1991

Kinetics of the urea-induced dissociation of human plasma alpha 2-macroglobulin as measured by small-angle neutron scattering.

The kinetics of the urea-induced dissociation of human plasma alpha 2-macroglobulin into two half-molecular fragments was investigated at 21.0 degrees C by using small-angle neutron scattering. The relative change in molecular mass that occurs upon dissociation was monitored by recording the forward scattering of neutrons as a function of time. All these kinetic data can be explained by a reaction that is first-order with respect to the concentration of undissociated alpha 2-macroglobulin. The velocity constant is a function of urea concentration and it varies within wide limits. For instance, the half-life of the reaction at the lowest concentration of [2H]urea studied (2.70 M) is 328 h, whereas the same value at the highest concentration of [2H]urea (6.24 M) is only 8 min. Measurements were made both with [1H]urea in 1H2O and with [2H]urea in 99% 2H2O, and it was found that there is a pronounced kinetic isotope effect, i.e. the dissociation is 4 times faster in the 1H-containing medium as compared with the 2H-containing medium at the same molar concentration of urea. From the angular dependence of the neutron scattering it can be concluded that the dissociation is associated with a drastic change in structure. This is directly shown by the radius of gyration, which increases from about 7.4 nm immediately after the addition of urea up to about 9.4 nm when the protein is fully dissociated. A structural analysis shows that the scattering curve of urea-dissociated alpha 2-macroglobulin can best be explained by that of a Gaussian coil with a radius of gyration equal to 9.44 nm. These data indicate that the so-called non-covalent interaction of alpha 2-macroglobulin probably is more complicated than just a pure hydrophobic interaction. Finally, it is also shown that the dissociation is accompanied by a loss in trypsin-binding activity, which is directly related to the fraction of dissociated protein.

Animals↗
PubMed1991

Spatial arrangement of sigma-factor and core enzyme of Escherichia coli RNA polymerase. A neutron solution scattering study.

By means of neutron solution scattering we determined the position and orientation of core enzyme and sigma-factor within the Escherichia coli RNA polymerase holoenzyme with the aim of improving existing models. The individual components, core enzyme (E) and sigma-factor (sigma), were highlighted by deuterium labeling and their center-to-center distances determined in the monomeric and the dimeric holoenzyme. The following distance parameters were obtained: dE1-sigma 1 = 8.6(+/- 1) nm, dE1-E2 = 11.5(+/- 1) nm, d sigma 1-sigma 2 = 12.0(+/- 0.7) nm, dE1-sigma 2 = 9(+/- 3) nm. Using a triangulation procedure the position of the sigma-factors, sigma 1 and sigma 2, were determined with respect to the mass center of the core enzyme molecules, E1 and E2, assuming a symmetrical arrangement of the holoenzyme molecules in the dimer (C2 symmetry). In addition, the orientation of the sigma-factor with respect to core enzyme was estimated by means of model calculations. The obtained model of holoenzyme depicts the sigma-factor as buried in a groove of core enzyme, probably between the large subunits beta' and beta.

DNA-Directed RNA Polymerases↗
PubMed1991

Correlation between the human and porcine complement system: a small-angle scattering study of cross immunity and methylamine-induced conformational changes of porcine C3 and C4 proteins.

The porcine complement proteins C3 and C4 have been isolated and then characterized using small-angle scattering methods. Within the limits of experimental errors, the porcine proteins are virtually identical with the corresponding human proteins as measured in terms of mol. wt, Mr and radius of gyration, R,: Mr(C3) = 198,000, Mr(C4) = 207,000, and R(C3) = 4.4 nm, R(C4) = 4.5 nm. The C3 and C4 proteins from pigs show cross-immunity with monoclonal antibodies (mAbs) raised against human C3 and C4, respectively. Using the Fab fragments of these mAbs as markers, it is indicated that porcine C3 and C4 undergo a conformational change after reaction with methylamine. The relatively large increase in the radius of gyration observed, delta R = 1.0-1.2 nm, going from the Fab complexes to the Fab complexes of the methylamine derivatives, is similar to that observed for human C3 under similar conditions. This may indicate that methylamine cleaves a labile thiol ester bond supposed to be present within the porcine proteins and that the epitopes interacting with the Fab fragments are very similar to those of the human proteins. Porcine C3 also resembles the human analogue by forming dimers after being subjected to methylamine and dilute lauryl sulphate: Mr = 404,000 and R = 7.9 nm.

Animals↗
PubMed1991

Structural and functional domains of E coli initiation factor IF2.

Initiation of translation in prokaryotes requires the participation of at least three soluble proteins: the initiation factors IF1, IF2 and IF3. Initiation factor 2, which is one of the largest proteins involved in translation (97.3 kDa) has been shown to stimulate in vitro the binding of fMet-tRNA(fMet) to the 30S ribosomal subunit. After formation of 70S translation initiation complex, IF2 is believed to participate in GTP hydrolysis, thereby promoting its own release. Here we review evidence which indicates the functional importance of the different structural domains of IF2, emphasizing new information obtained by in vivo experiments.

Amino Acid Sequence↗
PubMed1990

Structure of a RecA-DNA complex from linear dichroism and small-angle neutron-scattering in flow-oriented solution.

Small-angle neutron-scattering (SANS) and ultraviolet linear dichroism (l.d.) were measured on identical samples of a RecA-double-stranded (ds) DNA complex, including cofactor adenosine 5'-O-thiotriphosphate, which were aligned by flow in two equivalent Couette devices made of niobium and silica, transparent to neutrons and to ultraviolet light, respectively. The SANS anisotropy indicates a modest orientation of the RecA-dsDNA fiber with the helix axis parallel to the flow field. By correlation with the corresponding l.d. of the DNA at the same orientation conditions, it is inferred that the DNA bases have a local orientation that is approximately perpendicular to the helix axis. By comparison with the worse orientation in single-stranded DNA-RecA, this conclusion suggests that the dsDNA in its complex with RecA is not strand separated, and may be accommodated as an essentially unperturbed, straight double helix running along the RecA polymer fiber. The SANS anisotropy is also found to support the assignment of a subsidiary intensity maximum as originating from the pitch of a helical fiber.

Animals↗
PubMed1990

The H(+)-induced dissociation of human plasma alpha 2-macroglobulin. An investigation using small-angle neutron scattering and test of trypsin binding activity.

The dissociation of the tetrameric alpha 2-macroglobulin molecule into two half-molecular fragments, which occurs at pH less than 4.5, has been investigated using the small-angle neutron scattering method, and test of trypsin binding activity. Best fit with the relative forward scattering of neutrons is obtained for a model where the dissociation of the protein is driven by the uptake of H+ on altogether four acid-base groups, one per monomeric subunit of alpha 2-macroglobulin. These groups are not (or only slightly) accessible in the native tetramer, but become exposed to the solvent after dissociation of the protein. The H(+)-binding constant obtained for these groups, after dissociation of the protein, log K1 in the range 4.2-4.5, suggests that they are most probably carboxylate groups. From the about 10% increase in the radius of gyration, which occurs when lowering the pH from 4.5 to 2.0, we can conclude that the dissociation is associated with a change in structure of the protein. Tests of trypsin binding show that there is also an irreversible loss in trypsin binding activity, which is directly related to the fraction of dissociated protein. Thus, at pH less than 4.5, there is a transition of alpha 2-macroglobulin which results simultaneously in dissociation, disorganisation of the conformation of the subunits and loss in activity.

Binding Sites↗