Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling

The ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) plays a central role in the cellular response to changes in oxygen availability. pVHL binds to HIF only when a conserved proline in HIF is hydroxylated, a modification that is oxygen-dependent. The 1.85 angstrom structure of a 20-residue HIF-1alpha peptide-pVHL-ElonginB-ElonginC complex shows that HIF-1alpha binds to pVHL in an extended beta strand-like conformation. The hydroxyproline inserts into a gap in the pVHL hydrophobic core, at a site that is a hotspot for tumorigenic mutations, with its 4-hydroxyl group recognized by buried serine and histidine residues. Although the beta sheet-like interactions contribute to the stability of the complex, the hydroxyproline contacts are central to the strict specificity characteristic of signaling.     

Harnessing attosecond science in the quest for coherent X-rays

Modern laser technology has revolutionized the sensitivity and precision of spectroscopy by providing coherent light in a spectrum spanning the infrared, visible, and ultraviolet wavelength regimes. However, the generation of shorter-wavelength coherent pulses in the x-ray region has proven much more challenging. The recent emergence of high harmonic generation techniques opens the door to this possibility. Here we review the new science that is enabled by an ability to manipulate and control electrons on attosecond time scales, ranging from new tabletop sources of coherent x-rays to an ability to follow complex electron dynamics in molecules and materials. We also explore the implications of these advances for the future of molecular structural characterization schemes that currently rely so heavily on scattering from incoherent x-ray sources.     

National character does not reflect mean personality trait levels in 49 cultures

Most people hold beliefs about personality characteristics typical of members of their own and others' cultures. These perceptions of national character may be generalizations from personal experience, stereotypes with a "kernel of truth," or inaccurate stereotypes. We obtained national character ratings of 3989 people from 49 cultures and compared them with the average personality scores of culture members assessed by observer ratings and self-reports. National character ratings were reliable but did not converge with assessed traits. Perceptions of national character thus appear to be unfounded stereotypes that may serve the function of maintaining a national identity.     

Epoxide-opening cascades promoted by water

Selectivity rules in organic chemistry have been inferred largely from nonaqueous environments. In contrast, enzymes operate in water, and the chemical effect of the medium change remains only partially understood. Structural characterization of the "ladder" polyether marine natural products raised a puzzle that persisted for 20 years: Although the stereochemistry of adjacent tetrahydropyran (THP) cycles would seem to arise from a biosynthetic cascade of epoxide-opening reactions, experience in organic solvents argued consistently that such a pathway would be kinetically disfavored. We report that neutral water acts as an optimal promoter for the requisite ring-opening selectivity, once a single templating THP is appended to a chain of epoxides. This strategy offers a high-yielding route to the naturally occurring ladder core and highlights the likely importance of aqueous-medium effects in underpinning certain noteworthy enzymatic selectivities.     

Chankillo: a 2300-year-old solar observatory in coastal Peru

The Thirteen Towers of Chankillo run north to south along a low ridge within a fourth-century B.C.E. ceremonial complex in north coastal Peru. From evident observing points within the adjacent buildings to the west and east, they formed an artificial toothed horizon that spanned-almost exactly-the annual rising and setting arcs of the Sun. The Chankillo towers thus provide evidence of early solar horizon observations and of the existence of sophisticated Sun cults, preceding the Sun pillars of Incaic Cusco by almost two millennia.     

Mass spectrometry of intact V-type ATPases reveals bound lipids and the effects of nucleotide binding

The ability of electrospray to propel large viruses into a mass spectrometer is established and is rationalized by analogy to the atmospheric transmission of the common cold. Much less clear is the fate of membrane-embedded molecular machines in the gas phase. Here we show that rotary adenosine triphosphatases (ATPases)/synthases from Thermus thermophilus and Enterococcus hirae can be maintained intact with membrane and soluble subunit interactions preserved in vacuum. Mass spectra reveal subunit stoichiometries and the identity of tightly bound lipids within the membrane rotors. Moreover, subcomplexes formed in solution and gas phases reveal the regulatory effects of nucleotide binding on both ATP hydrolysis and proton translocation. Consequently, we can link specific lipid and nucleotide binding with distinct regulatory roles.     

A methylaspartate cycle in haloarchaea

Access to novel ecological niches often requires adaptation of metabolic pathways to cope with new environments. For conversion to cellular building blocks, many substrates enter central carbon metabolism via acetyl-coenzyme A (acetyl-CoA). Until now, only two such pathways have been identified: the glyoxylate cycle and the ethylmalonyl-CoA pathway. Prokaryotes in the haloarchaea use a third pathway by which acetyl-CoA is oxidized to glyoxylate via the key intermediate methylaspartate. Glyoxylate condensation with another acetyl-CoA molecule yields malate, the final assimilation product. This cycle combines reactions that originally belonged to different metabolic processes in different groups of prokaryotes, which suggests lateral gene transfer and evolutionary tinkering of acetate assimilation. Moreover, it requires elevated intracellular glutamate concentrations, as well as coupling carbon assimilation with nitrogen metabolism.     

Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis

The Golgi enzyme beta1,6 N-acetylglucosaminyltransferase V (Mgat5) is up-regulated in carcinomas and promotes the substitution of N-glycan with poly N-acetyllactosamine, the preferred ligand for galectin-3 (Gal-3). Here, we report that expression of Mgat5 sensitized mouse cells to multiple cytokines. Gal-3 cross-linked Mgat5-modified N-glycans on epidermal growth factor and transforming growth factor-beta receptors at the cell surface and delayed their removal by constitutive endocytosis. Mgat5 expression in mammary carcinoma was rate limiting for cytokine signaling and consequently for epithelial-mesenchymal transition, cell motility, and tumor metastasis. Mgat5 also promoted cytokine-mediated leukocyte signaling, phagocytosis, and extravasation in vivo. Thus, conditional regulation of N-glycan processing drives synchronous modification of cytokine receptors, which balances their surface retention against loss via endocytosis.     

Organic-geochemical Differentiation of Petroleum-type Pollutants and Study of Their Fate in Danube Alluvial Sediments and Corresponding Water (Pančevo Oil Refinery, Serbia)

A review is given in this paper of the up-to-date results observed in differentiation and transformation studies on petroleum-type pollutants in underground and surface waters. Water and particulate matter derived from the locality of Pan?evo Petroleum Refinery, Serbia (River Danube alluvial formations). It was shown that distributions of n-alkanes, steranes and triterpanes, and δ¹³C_PDB values of n-alkanes may successfully be used for qualitatively differentiating the petroleum-type pollutants from native organic matter in recent sedimentary formations. In underground waters, a petroleum-type pollutant is exposed to microbiological degradation which is manifested through relatively fast degradation of n-alkanes. Following an almost complete degradation of crude oil n-alkanes in underground water, the biosynthesis of novel, even carbon-number C₁₆–C₃₀ n-alkanes may be observed. It is shown that the n-alkane distribution observed in a petroleum-type pollutant may depend on the intensity of its previous interaction with water. The fate of petroleum-type pollutants in environmental waters may be predicted through laboratory simulative microbiological degradation experiments by using microorganism consortiums similar to those observed under relevant natural conditions, as well as on corresponding nutrient base.     

Spatial and vertical distribution of <Superscript>137</Superscript>Cs in soils in the erosive area of southeastern Serbia (Pčinja and South Morava River Basins)

Purpose

The area of southeastern Serbia, the P?inja and South Morava River Basins, is under the influence of very strong erosion, and the aim of this study was to investigate the vertical and spatial distribution of the ¹³⁷Cs in the eroded soils of this area.

Materials and methods

Vertical soil profiles were collected with 5-cm increments from the uppermost layer down to 20, 25, 30, 40, and 50 cm of depth, depending on the thickness of the soil layers, i.e., down to the underlying parent rocks. Measurements of ¹³⁷Cs activity concentration were performed by using the HPGe gamma-ray spectrometer ORTEC-AMETEK (34 % relative efficiency and high resolution 1.65 keV at 1.33 MeV for ⁶⁰Co), from its gamma-ray line at 661.2 keV.

Results and discussion

The mean ¹³⁷Cs activity concentration across all 18 soil profiles (for all soil layers) was found to be 20 Bq kg^?1. In the greatest number of soil profiles, the ¹³⁷Cs activity concentration was generally highest in the first soil layer (0–5 cm) and decreased with soil depth, while in a few soil profiles, the peak of either the ¹³⁷Cs activity concentration occurred in the second soil layer (5–10 cm) or the ¹³⁷Cs activity concentration was almost equal throughout the entire soil profile. The mean ¹³⁷Cs activity concentration in the first soil layer (0–5 cm) was found to be 61 Bq kg^?1, and the high coefficient of variation of 92 % pointed out high spatial variability and large range of the ¹³⁷Cs activity concentrations in the study area.

Conclusions

The obtained results indicate that in the greatest number of soil profiles, ¹³⁷Cs is present in the upper layers, with concentration decreasing with depth, as is typical in uncultivated soil. Its spatial distribution was very uneven among the surface soil layers of the investigated sites. One of the main reasons for such pattern of ¹³⁷Cs in the study area may be soil erosion. Additional investigations which would support this hypothesis are required.