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Purification and functional analysis of a novel leucine-zipper/nucleotide-fold protein, BZAP45, stimulating cell cycle regulated histone H4 gene transcription.

Regulation of histone gene transcription at the G1/S phase transition via the Site II cell cycle control element is distinct from E2F-dependent mechanisms operative at the growth factor-related restriction point. E2F-independent activation of histone H4 gene expression combines contributions of several promoter factors, including HiNF-M/IRF2 and the HiNF-D/CDP-cut complex which contains pRB, CDK1, and cyclin A as non-DNA binding subunits. Mutational analyses suggest additional rate-limiting factors for Site II function. Using sequence-specific Site II DNA affinity chromatography, we identified a 45 kDa protein (KIAA0005 or BZAP45) that is embryonically expressed and phylogenetically conserved. Based on amino acid sequence analysis, BZAP45 contains a unique decapeptide that is part of a putative leucine-zipper protein with a nucleotide (ATP or GTP) binding fold. Bacterial expression of a full-length cDNA produces a 45 kDa protein. Binding studies reveal that highly purified BZAP45 does not interact with Site II, suggesting that BZAP45 function may require partner proteins. Forced expression of BZAP45 strongly stimulates H4 promoter (nt -215 to -1)/CAT reporter gene activity. Deletion analyses and point mutations indicate that BZAP45 enhances H4 gene transcription through Site II. Thus, BZAP45 is a novel regulatory factor that contributes to transcriptional control at the G1/S phase transition.

Binding Sites↗

Knowledge, attitudes, and practices on hypertension in a country in epidemiological transition.

Assessment of knowledge, attitudes, and practices (KAP) is a crucial element of hypertension control, but little information is available from developing countries where hypertension has lately been recognized as a major health problem. Therefore, we examined KAP on hypertension in a random sample of 1067 adults aged 25 to 64 years from the Seychelles Islands (Indian Ocean). KAP were assessed from an administered structured questionnaire. The age-standardized prevalence of hypertension (screening blood pressure [BP] > or = 160/95 mm Hg or taking antihypertensive medication) was 36% in men and 25% in women aged 25 to 64 years. Among hypertensive persons, 50% were aware of the condition, 34% were treated, and 10% had controlled BP (ie, BP <160/95 mm Hg). Most persons, whether nonhypertensive, unaware hypertensive, or aware hypertensive, had good basic knowledge related to hypertension determinants and consequences, possibly an effect of a nationwide cardiovascular disease prevention program over the last years. However, favorable outcome expectation, positive attitudes, and appropriate practices for hypertension and relevant healthy lifestyles were found in smaller proportions of participants, with little difference between aware hypertensives, unaware hypertensives, and nonhypertensives. Furthermore, hypertensive persons with other concurrent cardiovascular risk factors affecting the overall heart risk knew well the detrimental effects of these other factors but reported making little actual change to control them (particularly regarding overweight and sedentary habits). These data point to the need to maximize the efficiency of hypertension prevention and control programs so that delay in achieving effective hypertension control is minimized in countries experiencing recent emergence of hypertension as a major public health problem.

Adult↗

Finite element analysis of Rayleigh wave interaction with finite-size, surface-breaking cracks.

The interaction of surface acoustic waves with finite-size, surface-breaking, semi-circular cracks is studied numerically, and experimentally. We focus on the behavior of the reflection coefficient of the Rayleigh wave from such cracks in the far field of the crack, when the depth of the crack is comparable to the wavelength of the interrogating surface wave. The cases in which the depth of the crack is much smaller or much larger compared to the wavelength have been extensively investigated by many authors and are not considered here except for validating the numerical and experimental results in these regimes. The theoretical, finite element, and experimental results presented are in very good agreement over the range were the crack depth is much smaller or much larger compared to the wavelength of the incident Rayleigh wave. In the transition regime, between these two limiting cases, only the finite element and experimental data show good agreement since the theoretical predictions are no longer applicable. In the high crack depth to wavelength ratio (a/lambda(R)) regime, the finite element and experimental results close to the crack approach the limiting value of the reflection coefficient from a 90 degrees corner.

Journal Article↗

Adenoviral-mediated gene therapy of human bladder cancer with antisense interleukin-8.

We previously demonstrated the importance of interleukin-8 (IL-8) as a mediator of angiogenesis, tumorigenicity, and metastasis of transitional cell carcinoma (TCC) of the bladder. In the present study, we evaluated the feasibility of adenoviral mediated antisense IL-8 gene transfer (Ad IL-8-AS) as therapy for established TCC. In vitro, Ad IL-8-AS inhibited endothelial cell proliferation and enhanced endothelial cell apoptosis. The highly metastatic human TCC cell line 253J B-V(R) was implanted into the subcutis of athymic nude mice, and intralesional therapy with Ad IL-8-AS commenced when the tumors reached a diameter between 5 and 7 mm. Tumor growth was significantly inhibited compared with therapy in controls (saline and beta-galactosidase adenovirus). Ad IL-8-AS therapy decreased the in vivo expression of IL-8 and matrix metalloproteinase type 9 (MMP-9), reduced microvessel density, and enhanced endothelial cell apoptosis. These results indicate that Ad IL-8-AS therapy targets both tumor cells and host endothelial cells resulting in endothelial cell apoptosis and significant inhibition of tumor growth.

Adenoviridae↗

Stable (long-bonded) dimers via the quantitative self-association of different cationic, anionic, and uncharged pi-radicals: structures, energetics, and optical transitions.

Unusual dimers with wide interplanar separations, that is, very long bonds with d(D) approximately 3.05 A, are common to the spontaneous self-association of various organic pi-radicals in solution and in the crystalline solid state, independent of whether they are derived from negatively charged anion radicals of planar electron acceptors (TCNE-*, TCNQ-*, DDQ-*, CA-*), positively charged biphenylene cation-radical (OMB+*), or neutral phenalene radical (PHEN*). All dimeric species are characterized by intense absorption bands in the near-IR region that are diagnostic of the charge-transfer transitions previously identified with intermolecular associations of various electron-donor/acceptor dyads. The extensive delocalizations of a pair of pi-electrons accord with the sizable values of (i) the enthalpies (-Delta H(D)) and entropies (-Delta S(D)) of pi-dimerization measured by quantitative UV-vis/EPR spectroscopies and (ii) the electronic coupling element H(ab) evaluated from the strongly allowed optical transitions, irrespective of whether the diamagnetic dimeric species bear a double-negative charge as in (TCNE)(2)(2-), (TCNQ)(2)(2-), (DDQ)(2)(2-), (CA)(2)(2-) or a double-positive charge as in (OMB)(2)(2+) or are uncharged as in (PHEN)(2). These long-bonded dimers persist in solution as well as in the solid state and suffer only minor perturbations with Delta d(D) < 10% from extra-dimer forces that may be imposed by counterion electrostatics, crystal packing, and so forth. The characteristic optical transitions in such diamagnetic two-electron dimers are shown to be related to those in the corresponding paramagnetic one-electron pimers of the same pi-radicals with their parent acceptor, both in general accord with Mulliken theory.

Journal Article↗

Equation of state for a partially ionized gas. II.

The derivation of equations of state for fluid phases of a partially ionized gas or plasma is addressed from a fundamental point of view. A spherical cellular model is deduced for the hot curve limit (or ideal Fermi gas). Next the Coulomb interactions are added to the spherical cellular model for general ionic charge Z. Then an independent electron model within a Z electron cell plus several many-body effects are employed. Numerical examples of the theory for several elements (H, Li, N, Na, K, Ni, Rb, Pd, Cs, and Er) are reported. These results reduce in various limits of temperature and density to the expected behavior. They display electron, localization-delocalization phase transitions of liquid-gas character. In the higher Z elements, a second possible critical point has been found. The critical pressure, electron density and temperature for the lower-density critical points seem to obey power laws as a function of Z.

Journal Article↗

Fertilization of Xenopus eggs imposes a complete translational arrest of mRNAs containing 3'UUAUUUAU elements.

The early embryonic development of Xenopus is mainly governed by post-transcriptional regulations until the mid-blastula transition. In this report, we present evidence demonstrating that fertilization of Xenopus eggs triggers a complete translational arrest of mRNAs containing UA-rich elements in their 3'-untranslated region. This control is maintained at least until the mid-blastula transition. Neither maturation nor pseudo-fertilization of the egg is sufficient for triggering this control, suggesting that components originating from the male gamete are involved in the mechanism. Moreover, this control is exerted whether the mRNA is polyadenylated or not.

Animals↗

The nutrition transition in South Korea.

BACKGROUND: An accelerating shift from infectious to noncommunicable diseases and concurrent shifts in diet, activity, and body composition are universal trends but are especially apparent in middle- and lower-income countries. A unique nutrition transition has occurred in South Korea, a country that modernized earlier than most Asian countries did. OBJECTIVE: The purpose of this analysis was to describe the South Korean nutrition transition, focusing on specific features that other countries might follow to retain the healthful elements of their traditional diets. DESIGN: We used secondary data on economics, dietary intake, anthropometry, and causes of death, including a series of comparable nationally representative dietary surveys (the National Nutrition Survey). RESULTS: The structure of South Korea's economy, along with the country's dietary and disease patterns, began an accelerated shift in the 1970s. Major dietary changes included a large increase in the consumption of animal food products and a fall in total cereal intake. Uniquely, the amount and rate of increase in fat intake have remained low in South Korea. South Korea also has a relatively low prevalence of obesity compared with other Asian countries with similar or much lower incomes. CONCLUSIONS: The nutrition transition in South Korea is unique. National efforts to retain elements of the traditional diet are thought to have shaped this transition in South Korea in the midst of rapid economic growth and the introduction of Western culture.

Adolescent↗

The rate of CpG mutation in Alu repetitive elements within the p53 tumor suppressor gene in the primate germline.

Cytosine to thymine transition mutations at the CpG dinucleotide are the most common point mutations in cancer and genetic disease. We calculated the in vivo rate of CpG mutation in the primate germline by deriving a primordial consensus sequence for an Alu repetitive element which inserted into intron 6 of the primate p53 gene 35 to 55 million years ago. Comparison of this primordial sequence to the Alu sequence in intron 6 of present-day primates was used to determine the nature and rate of mutations which occurred during evolution. We estimate the half-life of a CpG nucleotide to be 24 to 60 million years, and the rate constant for mutation at this dinucleotide to be 1.2 x 1O(-8) to 2.9 x 1O(-8) years(-1). These results were confirmed by the analysis of a second Alu sequence in intron 10 of the p53 gene. The in vivo mutation rate is at least 1250-fold slower than the in vitro chemical rate of 5-methylcytosine deamination in double-stranded DNA, showing that current estimates of CpG mutation repair have been significantly underestimated. Furthermore, the mutability of the CpG dinucleotide has led to the depletion of this dinucleotide from the vertebrate genome, and calculations in this study suggest that current levels of the CpG dinucleotide in the primate genome are very close to a steady state equilibrium in which the rate of CpG mutation is equal to the rate of CpG formation by random mutation.

Animals↗

Database-guided thermodynamic-kinetic regulation for PtNi-based intermetallic electrocatalysts.

Pt-Ni alloys exhibit outstanding oxygen reduction reaction (ORR) activity, yet achieving structural ordering to enhance stability remains a persistent challenge. Here, we propose a database-guided screening strategy to identify promoter elements (X) that facilitate ordering. By screening the critical disorder-to-order transition temperature ([Formula: see text]), solid solubility ([Formula: see text]), and diffusion pre-exponential factor ([Formula: see text]) of candidate elements from material databases, six sets of L10-Pt(NiX) nanoparticles were synthesized. The developed L10-PtNiFe catalysts demonstrated a high mass activity (MA) of 4.38 A mgPt-1, retaining 82.1% after 50,000 cycles of accelerated durability testing (ADT) in half-cells, and retaining 79% of its initial MA of 1.1 A mgPt-1 after 30,000 cycles in membrane electrode assembly (MEA). Theoretical calculations reveal that X incorporation broadens the annealing temperature ([Formula: see text]) window by forming Pt(NiX) with higher [Formula: see text] and lowering the kinetic threshold temperature ([Formula: see text]) via enhanced atom mobility. This work establishes a database-guided framework that enables phase transitions previously difficult to access by creating an effective annealing window through coordinated thermodynamic-kinetic regulation, thereby facilitating the formation of ordered PtNi-based intermetallic structures toward durable electrocatalysts.

Journal Article↗

Transition from spherical to deformed shapes of nuclei in the Monte Carlo shell model.

The transition from spherical to deformed shapes is studied in terms of large-scale shell-model calculations for Ba isotopes as a function of valence nucleon number with fixed single-particle space and Hamiltonian. A new version of the Monte Carlo shell model is introduced so as to incorporate pairing correlations efficiently, by utilizing condensed pair bases. The energy levels and electromagnetic matrix elements are described in agreement with experiments throughout the transitional region. The orbital M1 sum rule is calculated as a measure of the deformation evolution, and the Q-phonon picture is shown to be reasonable from spherical to deformed nuclei.

Journal Article↗

Self-organization in computer simulated selective systems.

In certain biologic systems, the signal selects functional or numerical expansion of the recognizing elements. Examples of these systems include the immune system, brain cortex, and evolution. One common feature of these Darwinian-type systems is degenerate recognition, in which one signal can recognize several different elements, with different affinities and consequences. For example, T cell antigen receptors and antibodies demonstrate relative but not absolute specificity of recognition. Thus, the variables of dose of the signal and affinity of the recognizing element modulate the outcome. Another feature of these systems is the ability to create self-organized patterns, which do not mirror the incoming signals. The hypothesis of this study is that degenerate recognition with subsequent selection of recognizing elements can explain self-organization of these systems. An entirely numerical model was explored, using the cellular automata approach. Three intrinsic features of a common selective system were incorporated into this model: a large number of recognizing elements; degenerative recognition of stimuli by these elements; and subsequent selection. Different numerical patterns of incoming stimuli were tested. The model showed self-organizing dynamics. Usually, the population of recognizing elements demonstrated an initial period of equilibrium, then a chaotic transitional state, and, finally, the bifurcational appearance of a stable self-organized pattern. The final resolution into a stable pattern can be either gradual or quasi-saltational. I conclude that systems with a large number of recognizing elements, degenerative recognition, and selection of recognizing elements can self organize based upon the pattern of the incoming stimuli.

Computer Simulation↗

Thrombus-in-transit and paradoxical embolism.

Paradoxical embolism is an uncommon but clinically important phenomenon. Elements of diagnosis include the presence of: (1) a venous thrombus, (2) an arterial embolus, (3) a communication between the right and left heart, and (4) a thrombus traversing such a communication. Unfortunately, all of these elements can be rarely demonstrated in each case but the probability should be considered in any patient with 2 or more present. It should be suspected in patients who have evidence of systemic arterial emboli without apparent cause. A transesophageal echocardiogram with contrast should be considered in cases where paradoxical embolism is a possibility. We present a case in which a "thrombus-in-transit" was imaged across the interatrial septum in a patient with a patent foramen ovale, deep venous thrombosis, and an embolic cerebrovascular stroke.

Aged↗

Contribution to the knowledge of infectivity of Fasciola hepatica adolescariae after their passage through the digestive tract of white mice.

The study of infective elements of Fasciola hepatica which passed through the digestive tract of white mice revealed that those adolescariae (transitive adolescariae) (Table 1), which were not visibly damaged or possessed a more or less digested outer cyst wall, remained infective. The mice infected with transitive adolescariae harboured higher number of trematodes in the livers than those infected with infective elements which had not previously passed through the digestive tract of the definitive host.

Animals↗

Paedogenesis in european newts (Triturus: salamandridae): cranial morphology during ontogeny.

A cross-sectional analysis using different ontogenetic stages (larvae, juveniles, paedotypic, and metamorphic adults) of the smooth newt, Triturus vulgaris, and the alpine newt, T.alpestris, revealed a broad spectrum of perennibranchiation influences on cranial ontogeny in European newts, more pronounced than previously thought. These influences included marked variation in ossification levels, pronounced morphometric variability of many cranial elements, and considerable skull shape changes in the transition from larvae to the adult stage. In comparison with metamorphosed individuals, paedotypic newts had a higher level of variability in both individual cranial traits and cranial shape changes. Sexual size difference of the skull traits was mostly negligible, especially in comparison to the influence of paedogenesis. The main changes in cranial shape of the European newts occurred during metamorphosis. Cranial morphological organization in the majority of examined paedotypes corresponds to cranial organization at late larval stages prior to metamorphosis or at the onset of metamorphosis.

Animals↗

Supported absorption of CO2 by tetrabutylphosphonium amino acid ionic liquids.

A new type of "task specific ionic liquid", tetrabutylphosphonium amino acid [P(C4)4][AA], was synthesized by the reaction of tetrabutylphosphonium hydroxide [P(C4)4][OH] with amino acids, including glycine, L-alanine, L-beta-alanine, L-serine, and L-lysine. The liquids produced were characterized by NMR, IR spectroscopies, and elemental analysis, and their thermal decomposition temperature, glass transition temperature, electrical conductivity, density, and viscosity were recorded in detail. The [P(C4)4][AA] supported on porous silica gel effected fast and reversible CO2 absorption when compared with bubbling CO2 into the bulk of the ionic liquid. No changes in absorption capacity and kinetics were found after four cycles of absorption/desorption. The CO2 absorption capacity at equilibrium was 50 mol % of the ionic liquids. In the presence of water (1 wt %), the ionic liquids could absorb equimolar amounts of CO2. The CO2 absorption mechanisms of the ionic liquids with and without water were different.

Journal Article↗

X-ray structure of recombinant ricin A-chain at 1.8 A resolution.

Ricin is a potent plant toxin which acts by removing a specific adenine residue from the ribosome. The X-ray crystal structure of a new, tetragonal crystal form of the recombinant ricin A-chain diffracting to 1.8 A resolution has been determined via molecular replacement methods and refined to a crystallographic R-factor of 18.6%. The higher resolution electron density allowed improvements to be made upon previously published models, resulting in an increase in the assigned secondary structure of the protein. The enzyme adopts the same global conformation in this crystal form with differences in detail due only partly to crystal packing. The active site superimposes closely with those of previously published models but the locations of the active-site water molecules differ in this structure. To address the current mechanistic model, an additional two structures are presented: recombinant ricin A-chain complexed with the substrate analogue formycin monophosphate as well as with adenosine monophosphate, which is cleaved by the crystalline enzyme. The formycin monophosphate displaces a putative catalytic water molecule. This supports the notion that the analogue does not bind in a transition state conformation and that contacts from other elements of the 28 S RNA natural substrate are required to achieve full reactivity. The structure of the adenosine monophosphate complex suggests a mechanism for the release of the adenine product via of the side-chain Tyr80. The structures suggest that Glu177 is better positioned for the activation of the catalytic water molecule than Arg180.

Adenosine Monophosphate↗

Osteoclast-like giant cell tumour of the gallbladder.

We describe a rare carcinoma of the gallbladder containing osteoclast-like giant cells. Well-differentiated adenocarcinoma was found in the mucosa of the fundus, and osteoclast-like giant cells were present mainly in a haemorrhagic mass protruding from the mucosal surface. The metastatic hepatic tumour was composed chiefly, if not exclusively, of osteoclastoma-like cells, but minute carcinomatous elements were also present. There was an apparent transition between the giant cells and tubular structures in both the gallbladder tumour and hepatic tumour. However, ultrastructural study did not reveal any evidence of epithelial differentiation in the giant cells. Immunohistochemical studies suggested that the mononuclear and giant cells were mesenchymal and histiocytic in nature (vimentin and factor XIIIa positive). A few exceptional giant cells transforming from the fine tubular structure were positive for epithelial membrane antigen. In conclusion, the osteoclast-like giant cell tumour component was thought to represent mesenchymal metaplasia in pre-existent adenocarcinoma.

Adenocarcinoma↗