Geochronology and geochemistry data for the Elbrus, Tyrnyauz, and Chegem magmatic centers, Greater Caucasus, Russia.

The dataset presented here is associated with the article "Young Silicic Magmatism of the Greater Caucasus, Russia with implication for its delamination origin based on zircon petrochronology and thermomechanical modeling" [1]. We present detailed sample descriptions and source locations for the rocks from the Chegem, Tyrnyauz, and Elbrus volcanic center localities presented in that study. The dataset presents extensive isotope and trace element geochemistry of zircon crystals from these rocks, major phenocrysts, and whole rock O and H isotopic and elemental compositions. Zircon ages, trace element compositions, and Hf and O isotopic compositions were obtained by both laser ablation ICP-MS and secondary ionization mass spectrometry in situ techniques and chemical abrasion isotope dilution-thermal ionization mass spectrometry techniques. We also present whole-rock major element compositions obtained by X-ray fluorescence and trace element compositions obtained by solution inductively-coupled plasma mass spectrometry. We also report δ18O analyses of phenocrysts and groundmass in samples, δ18O-δ13C analyses of limestones and limestone xenoliths in the Chegem ignimbrite, and coupled δ18O-δD-Δ17O analyses of glass and groundmass of rock samples from the Chegem ignimbrites that show abundant evidence of post-emplacement interaction with meteoric waters. To supplement the associated study [1], this article also includes field photographs, cathodoluminescence images of zircons, plots of trace element compositions in zircon, plots of stable isotopic variations in Chegem ignimbrites vs. stratigraphy, and selected trace elemental whole-rock diagrams.

Pervasive Hydrothermal Events Associated with Large Igneous Provinces Documented by the Columbia River Basaltic Province.

The degree and extent of crustal hydrothermal alteration related to the eruption of large igneous provinces is poorly known and not easily recognizable in the field. We here report a new δ18O dataset for dikes and lavas from the Columbia River Basalt Group (16-15 Ma) in the western USA, and document that dikes on average are 1-2‰ more depleted in δ18O than basalt flows. We show that this observation is best explained with the involvement of heated meteoric  waters during their cooling in the crust. The largest 6-8‰ depletion is found around and inside a 10 m-thick feeder dike that intruded the 125 Ma Wallowa tonalitic batholith. This dike likely operated as a magma conduit for 4-7 years, based on the extent of heating and melting its host rocks. We show that this dike also created a hydrothermal system around its contacts extending up to 100 m into the surrounding bedrock. A model that considers (a) hydrothermal circulation around the dike, (b) magma flow and (c) oxygen isotope exchange rates, suggests that the hydrothermal system operated for ~150 years after the cessation of magma flow. In agreement with a previously published (U-Th)/He thermochronology profile, our model shows that rocks 100 m away from such a dike can be hydrothermally altered. Collectively, our sample set is the first documentation of the widespread hydrothermal alteration of the shallow crust caused by the intrusion of dikes and sills of the Columbia River Basalt Province. It is estimated that heating and hydrothermal alteration of sediments rich in organic matter and carbonates around the dikes and sills releases 18 Gt of greenhouse gases (CH4 and CO2). Furthermore, hydrothermal δ18O depletion of rocks around dikes covers 500-600 km3, which, when scaled to the total CRB province constitutes 31,000 km3 of low-δ18O rocks. These volumes of crust depleted in δ18O are sufficient to explain the abundant low-δ18O magmas in eastern Oregon and western Idaho. This work also demonstrates that the width and magnitude of δ18O depletion around dikes can identify them as feeders. Given this, we here interpret Paleoproterozoic dikes in Karelia with the world's lowest δ18O depletions (-27.8‰) as feeders to the coeval large igneous province aged 2.2-2.4 Ga that operated under the Snowball Earth glaciation conditions.

Repression of BIM mediates survival signaling by MYC and AKT in high-risk T-cell acute lymphoblastic leukemia.

Treatment resistance in T-cell acute lymphoblastic leukemia (T-ALL) is associated with phosphatase and tensin homolog (PTEN) deletions and resultant phosphatidylinositol 3'-kinase (PI3K)-AKT pathway activation, as well as MYC overexpression, and these pathways repress mitochondrial apoptosis in established T-lymphoblasts through poorly defined mechanisms. Normal T-cell progenitors are hypersensitive to mitochondrial apoptosis, a phenotype that is dependent on the expression of proapoptotic BIM. In a conditional zebrafish model, MYC downregulation induced BIM expression in T-lymphoblasts, an effect that was blunted by expression of constitutively active AKT. In human T-ALL cell lines and treatment-resistant patient samples, treatment with MYC or PI3K-AKT pathway inhibitors each induced BIM upregulation and apoptosis, indicating that BIM is repressed downstream of MYC and PI3K-AKT in high-risk T-ALL. Restoring BIM function in human T-ALL cells using a stapled peptide mimetic of the BIM BH3 domain had therapeutic activity, indicating that BIM repression is required for T-ALL viability. In the zebrafish model, where MYC downregulation induces T-ALL regression via mitochondrial apoptosis, T-ALL persisted despite MYC downregulation in 10% of bim wild-type zebrafish, 18% of bim heterozygotes and in 33% of bim homozygous mutants (P=0.017). We conclude that downregulation of BIM represents a key survival signal downstream of oncogenic MYC and PI3K-AKT signaling in treatment-resistant T-ALL.

Molecular recognition of acute myeloid leukemia using aptamers.

Cell surface proteins can play important roles in cancer pathogenesis. Comprehensive understanding of the surface protein expression patterns of tumor cells and, consequently, the pathogenesis of tumor cells depends on molecular probes against these proteins. To be used effectively for tumor diagnosis, classification and therapy, such probes would be capable of specific binding to targeted tumor cells. Molecular aptamers, designer DNA-RNA probes, can address this challenge by recognizing proteins, peptides and other small molecules with high affinity and specificity. Through a process known as cell-based SELEX, we used live acute myeloid leukemia (AML) cells to select a group of DNA aptamers, which can recognize AML cells with dissociation constants (Kd's) in the nanomolar range. Interestingly, one aptamer (KH1C12) compared with two control cell lines (K562 and NB4) showed significant selectivity to the target AML cell line (HL60) and could recognize the target cells within a complex mixture of normal bone marrow aspirates. The other two aptamers KK1B10 and KK1D04 recognize targets associated with monocytic differentiation. Our studies show that the selected aptamers can be used as a molecular tool for further understanding surface protein expression patterns on tumor cells and thus providing a foundation for effective molecular analysis of leukemia and its subcategories.

Sediment-associated reactions of aromatic amines. 1. Elucidation of sorption mechanisms.

Sorption of aromatic amines to sediments and soils can occur by both reversible physical processes and irreversible chemical processes. To elucidate the significance of these sorption pathways, the sorption kinetics of aniline and pyridine were studied in resaturated pond sediment. Aniline and pyridine behaved quite differently in the sediment-water systems. The sorption kinetics of pyridine were quite fast, reaching equilibrium within 1-2 h. In contrast, the sorption kinetics of aniline were characterized by a rapid initial loss of aniline from the aqueous phase followed by a much slower rate of disappearance. The rapid initial sorption of aniline upon respiking after an equilibration period of 200 h, and results of sorption kinetic studies as a function of substrate concentration, demonstrated that sorptive sites were not being saturated at the nominal concentration of aniline. Sequential extraction of a sediment treated with 14C-labeled pyridine and aniline suggested that pyridine was bound primarily through a reversible cation-exchange process, whereas aniline sorbed through both cation-exchange and covalent binding processes. At longer reaction periods sorption became increasingly dominated by covalent binding. The reaction kinetics for the slow, irreversible sorption of aniline appeared to be limited by the reactivity and/or availability of covalent binding sites. The initial rate and extent of aniline sorption was pH dependent (sorption increased with decreasing pH). At pH values above the pKa of aniline, sorption kinetics for the slower, irreversible loss of aniline were independent of pH.

Synthesis and structure-activity relationships of retinoid X receptor selective diaryl sulfide analogs of retinoic acid.

Retinoids exert their biological effects by binding to and activating nuclear receptors that interact with responsive elements on DNA to promote gene transcription. There are two families of retinoid receptors, the retinoic acid receptor (RAR) family and the retinoid X receptor (RXR) family, which are each further divided into three subclasses: RAR alpha, beta, gamma and RXR alpha, beta, gamma. Herein we describe the synthesis and structure-activity relationships of a new series of diaryl sulfide retinoid analogs that specifically bind and transactivate the RXRs. Furthermore, the sulfoxide and sulfone derivatives of these analogs are partial agonists which activate the RXRs only at high concentrations. Thus, these compounds possess a potential site of metabolic deactivation and may have less prolonged systemic effects than other compounds with arotinoid-like structures. We show also that these compounds have activity in nontransfected cells as demonstrated by their ability to induce TGase activity in HL-60 cells. Finally, we corroborate our earlier report that RXR-specific agonists may possess reduced teratogenic toxicity compared to RAR-specific agonists since these compounds are much less potent inhibitors of chondrogenesis than RAR-specific agonists such as TTNPB.

Synthesis and structure-activity relationships of stilbene retinoid analogs substituted with heteroaromatic carboxylic acids.

Retinoids elicit biological responses by activating a series of nuclear receptors. Six retinoid receptors belonging to two families are currently known: retinoic acid receptors (RAR alpha,beta,and gamma) and retinoid X receptors (RXR alpha,beta,and gamma). Stilbene retinoid analogs of retinoic acid (RA), such as (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)prope n-1- yl]benzoic acid (TTNPB, 1) and (E)-4-[2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)pro pen-1- yl]benzoic acid (3-methyl-TTNPB, 2), display differential RAR and RXR activities, depending on the substituent at C3 of the naphthalene ring. We report here structural modifications of the benzoate moiety of 2 that result in analogs with greater RXR selectivity as well as those with pan-agonist (activate both RAR and RXR receptors) activities, analyze the structural features that impart receptor selectivity, and describe a stereoselective method for the synthesis of these analogs. The biological activities associated with the RAR and RXR receptors were examined by testing representative examples with different receptor activation profiles for their ability to induce tissue transglutaminase (Tgase) activity in a human promyelocytic leukemia cell line (HL-60 cdm-1) and to inhibit tumor-promoter-induced ornithine decarboxylase (ODC) activity in hairless mouse skin. These results suggest that RAR agonists and RXR agonists may have different therapeutic applications. Finally, we show that RXR agonists are significantly reduced in teratogenic potency relative to RAR agonists and may therefore have significant advantages in clinical practice.

Family handedness as a predictor of mental rotation ability among minority girls in a math-science training program.

Right-handed girls from nonright-handed families outperformed the other groups of minority adolescent girls enrolled in a science and technology program on a test of mental rotation ability. This target group excelled over right-handed girls with all right-handed relatives and nonright-handers. The pattern of group differences in mental rotation ability found here is consistent with those found for women with math-science training at the college level. The minority boys in the program outperformed the girls as a whole, but did not differ significantly from the right-handed girls with nonright-handed relatives. The present findings provide further support for the generality of Annett's genetic theory of handedness and brain organization, and for the interaction of genetic and environmental factors in accounting for individual differences in mental rotation ability.

[Determination of serum lysozyme in infants with septicemia]. / Determinación de lisozima sérica en lactantes con septicemia.

The literature on serum lysozyme was reviewed and the normal values for this enzyme were analyzed in 40 healthy children (control group) and 40 children with a clinical diagnosis of septicemia. The patients were 1 to 18 months old and were hospitalized in the H.P. of the C.M.N., I.M.S.S. In 12 of these, the blood cultures developed bacteria, while 26 were negative. It was found that the normal values varied in healthy children from 5 to 24 microgram/ml. In the group of infected patients, the values varied from 4.4 to 53.3 microgram/ml. The group of healthy patients (control) was compared with the infected patients and a significantly difference was found (p less than 0.05), although in some infected children the readings for lysozyme were normal. In all patients, lysozyme returned to normal when the infection cleared. The mortality rate in this study was 15 per cent. It is concluded that in patients with severe infection, the levels of lysozyme in the serum may the elevated, while in patients with clinical signs of septicemia with positive blood cultures, there is a rise in lysozyme.

Determinacion de lisozima serica en lactantes con septicemia. / Determination of serum lysozyme in infants with septicemia

Se revisa literatura sobre la lisozima serica y se analizan los valores normales de esta enzima en 40 ninos sanos (grupo control), y 40 ninos de 1 a 18 meses con diagnostico clinico de septicemia, internados en el Hospital de Pediatria del Centro Medico Nacional del IMSS. En 12 de estos, el hemocultivo desarrollo bacterias y en 28 fue negativo. Se encontro que los valores normales en ninos sanos variaron entre 5 y 21 ug/ml. En el grupo de pacientes infectados, variaron entre 4.4 y 57.3 ug/ml. Se comparo el grupo de pacientes sanos (control) con el de infectados encontrando diferencia significativa (p<0.05), aunque en algunos pacientes con infeccion grave las cifras de lisozima fueron normales.En todos los pacientes, la lisozima se normalizo posteriormente a la curacion. La letalidad en este estudio fue del 15 por ciento.Se concluye que en los pacientes con infeccion grave, los niveles de lisozima serica pueden encontrarse elevados y en pacientes con cuadro clinico de septicemia y hemocultivo positivo la lisozima se encuentra elevada