Anthropometric correlates of C-reactive protein among indigenous Siberians

C-reactive protein (CRP) is an inflammatory marker, which at low-level elevations is associated with increased cardiovascular risk. Although CRP has been extensively investigated in North American and European settings, few studies have measured CRP among non-Western groups. The present study used dried whole blood spot samples to examine high-sensitivity CRP concentrations among the Yakut (Sakha) of Siberia (85 females, 56 males; 18-58 years old). Our goals were: (1) to compare Yakut CRP concentrations with other populations; (2) to investigate sex differences; and (3) to explore anthropometric correlates of CRP. Results indicate that serum equivalent CRP concentrations are similar to those from industrializing nations, lower than US and European values, and greater than Japanese concentrations. Yakut men and women display similar CRP concentrations; however, CRP was significantly higher among men after adjustment for body fat, age, and smoking. Positive associations were documented between CRP and BMI, body fat, and central adiposity.     

Probing subtle coordination changes in the iron-quinone complex of photosystem II during charge separation,by the use of NO

The terminal electron acceptor of Photosystem II, PSII, is a linear complex consisting of a primary quinone, a non-heme iron(II), and a secondary quinone, Q(A)Fe(2+)Q(B). The complex is a sensitive site of PSII, where electron transfer is modulated by environmental factors and notably by bicarbonate. Earlier studies showed that NO and other small molecules (CN(-), F(-), carboxylate anions) bind reversibly on the non-heme iron in competition with bicarbonate. In the present study, we report on an unusual new mode of transient binding of NO, which is favored in the light-reduced state (Q(A)(-)Fe(2+)Q(B)) of the complex. The related observations are summarized as follows: (i) Incubation with NO at -30 degrees C, following light-induced charge separation, results in the evolution of a new EPR signal at g = 2.016. The signal correlates with the reduced state Q(A)(-)Fe(2+) of the iron-quinone complex. (ii) Cyanide, at low concentrations, converts the signal to a more rhombic form with g values at 2.027 (peak) and 1.976 (valley), while at high concentrations it inhibits formation of the signals. (iii) Electron spin-echo envelope modulation (ESEEM) experiments show the existence of two protein (14)N nuclei coupled to electron spin. These two nitrogens have been detected consistently in the environment of the semiquinone Q(A)(-) in a number of PSII preparations. (iv) NO does not directly contribute to the signals, as indicated by the absence of a detectable isotopic effect ((15)NO vs (14)NO) in cw EPR. (v) A third signal with g values (2.05, 2.03, 2.01) identical to those of an Fe(NO)(2)(imidazole) synthetic complex develops slowly in the dark, or faster following illumination. (vi) In comparison with the untreated Q(A)(-)Fe(2+) complex, the present signals not only are confined to a narrow spectral region but also saturate at low microwave power. At 11 K the g = 2.016 signal saturates with a P(1/2) of 110 microW and the g = 2.027/1.976 signal with a P(1/2) of 10 microW. (vii) The spectral shape and spin concentration of these signals is successfully reproduced, assuming a weak magnetic interaction (J values in the range 0.025-0.05 cm(-)(1)) between an iron-NO complex with total spin of (1)/(2) and the spin, (1)/(2), of the semiquinone, Q(A)(-). The different modes of binding of NO to the non-heme iron are examined in the context of a molecular model. An important aspect of the model is a trans influence of Q(A) reduction on the bicarbonate ligation to the iron, transmitted via H-bonding of Q(A) with an imidazole ligand to the iron.     

Murine gammaherpesvirus 68 open reading frame 45 plays an essential role during the immediate-early phase of viral replication

Murine gammaherpesvirus 68 (MHV-68) has been developed as a model for the human gammaherpesviruses Epstein-Barr virus and human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV), which are associated with several types of human diseases. Open reading frame 45 (ORF45) is conserved among the members of the Gammaherpesvirinae subfamily and has been suggested to be a virion tegument protein. The repression of ORF45 expression by small interfering RNAs inhibits MHV-68 viral replication. However, the gene product of MHV-68 ORF45 and its function have not yet been well characterized. In this report, we show that MHV-68 ORF45 is a phosphorylated nuclear protein. We constructed an ORF45-null MHV-68 mutant virus (45STOP) by the insertion of translation termination codons into the portion of the gene encoding the N terminus of ORF45. We demonstrated that the ORF45 protein is essential for viral gene expression immediately after the viral genome enters the nucleus. These defects in viral replication were rescued by providing ORF45 in trans or in an ORF45-null revertant (45STOP.R) virus. Using a transcomplementation assay, we showed that the function of ORF45 in viral replication is conserved with that of its KSHV homologue. Finally, we found that the C-terminal 23 amino acids that are highly conserved among the Gammaherpesvirinae subfamily are critical for the function of ORF45 in viral replication.     

Crystal structure of the hydroxyquinol 1,2-dioxygenase from Nocardioides simplex 3E, a key enzyme involved in polychlorinated aromatics biodegradation

Hydroxyquinol 1,2-dioxygenase (1,2-HQD) catalyzes the ring cleavage of hydroxyquinol (1,2,4-trihydroxybenzene), a central intermediate in the degradation of aromatic compounds including a variety of particularly recalcitrant polychloro- and nitroaromatic pollutants. We report here the primary sequence determination and the analysis of the crystal structure of the 1,2-HQD from Nocardioides simplex 3E solved at 1.75 A resolution using the multiple wavelength anomalous dispersion of the two catalytic irons (1 Fe/293 amino acids). The catalytic Fe(III) coordination polyhedron composed by the side chains of Tyr164, Tyr197, His221, and His223 resembles that of the other known intradiol-cleaving dioxygenases, but several of the tertiary structure features are notably different. One of the most distinctive characteristics of the present structure is the extensive openings and consequent exposure to solvent of the upper part of the catalytic cavity arranged to favor the binding of hydroxyquinols but not catechols. A co-crystallized benzoate-like molecule is also found bound to the metal center forming a distinctive hydrogen bond network as observed previously also in 4-chlorocatechol 1,2-dioxygenase from Rhodococcus opacus 1CP. This is the first structure of an intradiol dioxygenase specialized in hydroxyquinol ring cleavage to be investigated in detail.     

The emergence of obesity among indigenous Siberians

Once considered a disease of affluence and confined to industrialized nations, obesity is currently emerging as a major health concern in nearly every country in the world. Available data suggest that the prevalence rate of obesity has reached unprecedented levels in most developing countries, and is increasing at a rate that far outpaces that of developed nations. This increase in obesity has also been documented among North American circumpolar populations and is associated with lifestyle changes related to economic development. While obesity has not been well studied among indigenous Siberians, recent anthropological studies indicate that obesity and its associated comorbidities are important health problems.The present study examines recent adult body composition data from four indigenous Siberian populations (Evenki, Ket, Buriat, and Yakut) with two main objectives: 1) to determine the prevalence of overweight and obesity among these groups, and 2) to assess the influence of lifestyle and socioeconomic factors on the development of excess body fat. The results of this study indicate that obesity has emerged as an important health issue among indigenous Siberians, and especially for women, whose obesity rates are considerably higher than those of men (12% vs. 7%). The present study investigated the association between lifestyle and body composition among the Yakut, and documented substantial sex differences in lifestyle correlates of obesity. Yakut men with higher incomes and who owned more luxury consumer goods were more likely to have excess body fat while, among Yakut women, affluence was not strongly associated with overweight and obesity.     

GTPases of the prokaryotic translation apparatus

Bacterial protein synthesis involves four protein factors that belong to the GTPase family: IF2, EF-G, EF-Tu, and RF3. Their role in translation has attracted considerable interest over the recent decades. Cryoelectron microscopy has made it possible to monitor the dynamics of the ribosome upon binding of the translation factors, and biochemical findings have associated the structural data with functional changes in GTPases: the exchange of GDP for GTP, activation of GTPase, and changes in its conformation. The results have been used to construct models of GTPase action during prokaryotic translation. Data are accumulating that the ribosome simultaneously acts as a GDP/GTP exchange factor and a GTPase-activating factor for RF3, IF2, and EF-G. The review systematizes the most important experimental findings and theoretical models proposed for regulation of the functional cycle of prokaryotic translation GTPases.     

Evolutionary and genetic analyses of mitochondrial translation initiation factors identify the missing mitochondrial IF3 in S. cerevisiae

Mitochondrial translation is essentially bacteria-like, reflecting the bacterial endosymbiotic ancestry of the eukaryotic organelle. However, unlike the translation system of its bacterial ancestors, mitochondrial translation is limited to just a few mRNAs, mainly coding for components of the respiratory complex. The classical bacterial initiation factors (IFs) IF1, IF2 and IF3 are universal in bacteria, but only IF2 is universal in mitochondria (mIF2). We analyse the distribution of mitochondrial translation initiation factors and their sequence features, given two well-propagated claims: first, a sequence insertion in mitochondrial IF2 (mIF2) compensates for the universal lack of IF1 in mitochondria, and secondly, no homologue of mitochondrial IF3 (mIF3) is identifiable in Saccharomyces cerevisiae. Our comparative sequence analysis shows that, in fact, the mIF2 insertion is highly variable and restricted in length and primary sequence conservation to vertebrates, while phylogenetic and in vivo complementation analyses reveal that an uncharacterized S. cerevisiae mitochondrial protein currently named Aim23p is a bona fide evolutionary and functional orthologue of mIF3. Our results highlight the lineage-specific nature of mitochondrial translation and emphasise that comparative analyses among diverse taxa are essential for understanding whether generalizations from model organisms can be made across eukaryotes.