Proteolytic activation of proteose peptone component 3 by release of a C-terminal peptide with antibacterial properties.

The milk protein proteose peptone component 3 (PP3, also known as lactophorin) is a small phosphoglycoprotein, which is exclusively expressed in the lactating mammary gland. A 23-residue synthetic peptide (lactophoricin, Lpcin S), corresponding to the C-terminal amphipathic α-helix of PP3, has previously been shown to permeabilize membranes and display antibacterial activity. Lactophorin readily undergoes proteolytic cleavage in milk and during dairy processing, and it has been suggested that PP3-derived peptides are part of milk's endogenous defense system against bacteria. Here, we report that a 26-residue C-terminal peptide (Lpcin P) can be generated by trypsin proteolysis of PP3 and that structural and functional studies of Lpcin P indicate that the peptide has antibacterial properties. The Lpcin P showed α-helical structure in both anionic and organic solvents, and the amount of α-helical structure was increased in the presence of lipid vesicles. Oriented circular dichroism showed that Lpcin P oriented parallel to the membrane surface. However, the peptide permeabilized calcein-containing vesicles efficiently. Lpcin P displayed antibacterial activity against Streptococcus thermophilus, but not against Staphylococcus aureus and Escherichia coli. The PP3 full-length protein did not display the same properties, which could indicate that PP3 functions as a precursor protein that upon proteolysis, releases a bioactive antibacterial peptide.

Small-scale mantle convection produces stratigraphic sequences in sedimentary basins.

Cyclic sedimentary deposits link stratigraphic sequences that are now geographically distant but were once part of the same depositional environment. Some of these sequences occur at periods of 2 to 20 million years, and eustatic sea-level variations or regional tectonic events are likely causes of their formation. Using numerical modeling, we demonstrate that small-scale mantle convection can also cause the development of stratigraphic sequences through recurrent local and regional vertical surface movements. Small-scale convection-driven stratigraphic sequences occur at periods of 2 to 20 million years and correlate only at distances up to a few hundred kilometers. These results suggest that previous sequence stratigraphic analyses may contain erroneous conclusions regarding eustatic sea-level variations.

Glacial effects limiting mountain height.

The height of mountain ranges reflects the balance between tectonic rock uplift, crustal strength and surface denudation. Tectonic deformation and surface denudation are interdependent, however, and feedback mechanisms-in particular, the potential link to climate-are subjects of intense debate. Spatial variations in fluvial denudation rate caused by precipitation gradients are known to provide first-order controls on mountain range width, crustal deformation rates and rock uplift. Moreover, limits to crustal strength are thought to constrain the maximum elevation of large continental plateaus, such as those in Tibet and the central Andes. There are indications that the general height of mountain ranges is also directly influenced by the extent of glaciation through an efficient denudation mechanism known as the glacial buzzsaw. Here we use a global analysis of topography and show that variations in maximum mountain height correlate closely with climate-controlled gradients in snowline altitude for many high mountain ranges across orogenic ages and tectonic styles. With the aid of a numerical model, we further demonstrate how a combination of erosional destruction of topography above the snowline by glacier-sliding and commensurate isostatic landscape uplift caused by erosional unloading can explain observations of maximum mountain height by driving elevations towards an altitude window just below the snowline. The model thereby self-consistently produces the hypsometric signature of the glacial buzzsaw, and suggests that differences in the height of mountain ranges mainly reflect variations in local climate rather than tectonic forces.

Energy intake variability in free-living young children.

It has been suggested that young children regulate their daily energy intake very closely with highly stable day-to-day total energy intake. This hypothesis was developed on the basis of an experimental study of 15 children aged 26 to 62 months, which reported a within-subject coefficient of variation (CV) in daily energy intake of 10.4%. We tested the hypothesis that free-living energy intakes were highly stable on a day-to-day basis in a sample of free-living young children from Glasgow, Scotland. In 101 children (47 boys) aged 2.6-6.8 years, energy intake was measured using multiple-pass 24-h recalls. Within-subject CV was 19.2%, which was significantly higher than the 10.4% reported by previously Birch and colleagues (p<0.0001). In addition, we identified four other studies on free-living children with within-subject CVs ranging from 16.1-28.7%. This evidence indicates that young children show a wide intra-individual variation in day-to-day regulation of energy intake in a free-living environment.

Vibrationally resolved photoabsorption spectroscopy of red fluorescent protein chromophore anions.

Photoabsorption studies of red fluorescent protein chromophore anions have been performed at the ELISA electrostatic heavy-ion storage ring. The broad absorption band due to electronic excitation of the chromophores is tuned to a longer wavelength (redshifted) by extending the electronic conjugation of the molecule. A clear vibrational progression is resolved with E(vib) approximately 380 and 520 cm(-1) for two different forms of the chromophore. The vibrational modes correspond to collective motions of the entire molecular structure. It is argued that the excited electronic state has an equilibrium configuration far from that of the electronic ground state, i.e., poor Franck Condon overlap.

Does serum cholesterol contribute to vertebral bone loss in postmenopausal women?

Recent in vitro and animal studies suggest that cholesterol and its metabolites inhibit the functional activity of osteoblasts and thereby induce reduced bone mineralization. However, scant information is available on the clinical implication of these findings with special regard to postmenopausal bone loss. Therefore, the aim of the present study was to investigate cross-sectional and longitudinal associations between serum cholesterol, bone mineral density (BMD), and bone turnover in 340 postmenopausal women aged 50-75 years (mean 59 years), who were followed for 8.3 +/- 1.1 years. BMD in the lumbar spine, distal forearm, and total hip was measured by dual energy X-ray absorptiometry. Other study variables were physical measures, serum cholesterol, serum markers of bone turnover, and self-reported information on various risk factors for osteoporosis. At baseline, serum cholesterol showed significant negative correlation with BMD at the lumbar spine (r = -0.21, P < 0.0001) and distal forearm (r = -0.14, P = 0.013), but not at the hip. No associations of serum cholesterol with serum osteocalcin (r = 0.054, P = 0.317) and CTX (r = -0.027, P = 0.623) were, however, noted. After adjustment for age and BMI, the negative correlation remained significant at the lumbar spine (r = -0.16, P = 0.004), but not at the distal forearm (r = -0.018, P = 0.738). At the end of the 8-year follow-up, the correlation between serum cholesterol and spine BMD was not observed. Those with the largest increases in serum cholesterol, however, showed the greatest decreases in spine BMD independently of the changes in BMI (r = -0.16, P = 0.004). The correlation between the changes in serum cholesterol and the simultaneous changes in osteocalcin (r = 0.081, P = 0.140) and CTX (r = 0.042, P = 0.441) were statistically insignificant. Thus, our results suggest that the weak associations between spine BMD and serum cholesterol can be explained by the fact that both variables are simultaneously affected by estrogen deficiency rather than by a direct influence of serum cholesterol on osteoblast function.

Absorption spectrum of the green fluorescent protein chromophore anion in vacuo.

A sensitive photoabsorption technique for studies of gas-phase biomolecules has been used at the ELISA electrostatic heavy-ion storage ring. We show that the anion form of the chromophore of the green fluorescent protein in vacuo has an absorption maximum at 479 nm, which coincides with one of the two absorption peaks of the protein. Its absorption characteristics are therefore ascribed to intrinsic chemical properties of the chromophore. Evidently, the special beta-can structure of the protein provides shielding of the chromophore from the surroundings without significantly changing the electronic structure of the chromophore through interactions with amino acid side chains.

On the formation of radical dications of protonated amino acids in a "microsolution" of water or acetonitrile and their reactivity towards the solvent.

In high-energy collisions (50 keV) between O2 and protonated amino acids AH+, radical dications AH2+* are formed for A = Phe, His, Met, Tyr, and Trp. When solvated by water or acetonitrile (S), AH2+*(S)1,2 are formed for A = Arg, His, Met, Tyr, and Trp. The stability of the hydrogen-deficient AH2+* in the "microsolution" depends on the energetics of the electron transfer reaction AH2+* +S --> AH++S+*, the hydrogen abstraction reaction AH2+*+S --> AH2(2+)+[S-H]*, and the proton transfer reaction AH2+* + S --> A+*+SH+. Using B3LYP/ 6-311+G(2d,p)//B3LYP/6-31+G(d) model chemistry, we describe these three reactions in detail for A=Tyr and find that the first two reactions are unfavorable whereas the third one is favorable. However, energy is required for the formation of Tyr+* and SH+ from TyrH2+*(S) to overcome the Coulomb barrier, which renders the complex observable with a life-time larger than 5 micros. The ionization energy, IE, of TyrH+ is calculated to be 11.1 eV in agreement with an experimental measurement of 10.1+/-2.1 eV ([IE(CH3CN)+IE(Tyr)]/ 2); hydration further lowers the IE by 0.3 eV [IE(TyrH+(H2O) = 10.8 eV, calculated]. We estimate the ionization energies of TrpH+, HisH+, and MetH+ to be 10.1+/-2.1 eV, 12.4+/-0.2 eV, and 12.4+/-0.2 eV, and that of PheH+ to be larger than 12.6 eV.

Electron loss from multiply protonated lysozyme ions in high energy collisions with molecular oxygen.

We report on the electron loss from multiply protonated lysozyme ions Lys-Hn(n)+ (n = 7 - 17) and the concomitant formation of Lys-Hn(n+1)+. in high-energy collisions with molecular oxygen (laboratory kinetic energy = 50 x n keV). The cross section for electron loss increases with the charge state of the precursor from n = 7 to n = 11 and then remains constant when n increases further. The absolute size of the cross section ranges from 100 to 200 A2. The electron loss is modeled as an electron transfer process between lysozyme cations and molecular oxygen.

Anthelmintic screening of Zimbabwean plants traditionally used against schistosomiasis.

Extracts of 23 plant species used popularly against schistosomiasis in Zimbabwe were screened for their anthelmintic effect. Schistosomules of the trematode Schistosoma mansoni and cysticercoids of the cestode Hymenolepis diminuta were studied in vitro. The material consisted of 58 plant extracts, of which 37 killed the newly excysted cysticercoids within an hour, when incubated in a culture medium. Lethal concentrations varied from 0.8 to 103 mg/ml. All plant extracts showed activity against the tapeworms after 24 h. Ten of the best extracts were also tested against schistosomules. Five of these extracts showed activity. Lethal concentrations varied from 0.6 to 33.8 mg/ml of dry plant material. Extracts of stem and root from Abrus precatorius (Fabaceae), of root bark and leaves from Ozoroa insignis (Anacardiaceae) and of root bark from Zizyphus mucronata (Rhamnaceae) gave the best results against tapeworms. The best results against schistosomules were obtained with stem and root extracts from Abrus precatorius (Fabaceae) and stem bark from Elephantorrhiza goetzei (Mimosaceae). Although the activity of root and root bark extracts commonly used in traditional medicine was verified in this study, our results showed that also extracts from leaf and stem can be effective anthelmintics.

Aging, intergenerational distribution and public pension systems.

"This paper develops an intertemporal simulation model capable of addressing the macroeconomic and distributional effects of demographic shocks in a small open economy. Two sources of population aging are examined, viz. lower birth rates and prolonged expected lifetimes at retirement age. Due to strong expectational effects, both shocks are found to change average consumption in a downward direction, in the short run as well as in the long run. This effect is matched by a strong net acquisition of foreign assets. Furthermore, it turns out that the intergenerational distribution of the burden of adjusting to an aging population is strongly dependent on whether the benefit rate, the contribution rate, or the relative non-capital income of pensioners and workers is held fixed."