Gene rearrangements in bone marrow cells of patients with acute myelogenous leukemia

At diagnosis, clonal gene rearrangement probes {[}retinoic acid receptor (RAR)-alpha, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell receptor (TcR)-beta, myeloid lymphoid leukemia (MLL) or cytokine genes (GM-CSF, G-CSF, IL-3)] were detected in bone marrow samples from 71 of 153 patients with acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML) (58%) and in 30 patients with secondary AML (42%). In all cases with promyelocytic leukemia (AML-M3) RAR-alpha gene rearrangements were detected (n = 9). Gene rearrangements in the Ig-JH or the TcR-beta or GM-CSF or IL-3 or MLL gene were detected in 12, 10, 16 and 12% of the cases, respectively, whereas only few cases showed gene rearrangements in the M-bcr (6%) or G-CSF gene (3%). Survival of pAML patients with TcR-beta gene rearrangements was longer and survival of pAML patients with IL-3 or GM-CSF gene rearrangement was shorter than in patients without those rearrangements. No worse survival outcome was seen in patients with rearrangements in the MLL, Ig-JH or M-bcr gene. In remission of AML (CR), clonal gene rearrangements were detected in 23 of 48 cases (48%) if samples were taken once in CR, in 23 of 26 cases (88%) if samples were taken twice in CR and in 23 of 23 cases (100%) if samples were studied three times in CR. All cases with gene rearrangements at diagnosis showed the same kind of rearrangement at relapse of the disease (n = 12). Our data show that (1) populations with clonal gene rearrangements can be regularly detected at diagnosis, in CR and at relapse of AML. (2) Certain gene rearrangements that are detectable at diagnosis have a prognostic significance for the patients' outcome. Our results point out the significance of gene rearrangement analyses at diagnosis of AML in order to identify `poor risk' patients - independently of the karyotype. Moreover, the persistence of clonal cells in the further course of AML can be studied by gene rearrangement analysis. Copyright (C) 2000 S. Karger AG, Basel

Rational Design of Pore Size and Functionality in a Series of Isoreticular Zwitterionic Metal-Organic Frameworks

The isoreticular expansion and functionalization of charged-polarized porosity has been systematically explored by the rational design of 11 isostructural zwitterionic metal-organic frameworks (ZW-MOFs). This extended series of general structural composition {[M3F(L1)3(L2)1.5]·guests}n was prepared by employing the solvothermal reaction of Co and Ni tetrafluoroborates with a binary ligand system composed of zwitterionic pyridinium derivatives and traditional functionalized ditopic carboxylate auxiliary ligands (HL1·Cl = 1-(4-carboxyphenyl)-4,4′-bipyridinium chloride, Hcpb·Cl; or 1-(4-carboxyphenyl-3-hydroxyphenyl)-4,4′-bipyridinium chloride, Hchpb·Cl; and H2L2 = benzene-1,4-dicarboxylic acid, H2bdc; 2-aminobenzene-1,4-dicarboxylic acid, H2abdc; 2,5-dihydroxy-1,4-benzenedicarboxylic acid, H2dhbdc; biphenyl-4,4′-dicarboxylic acid, H2bpdc; or stilbene-4,4′-dicarboxylic acid, H2sdc). Single-crystal structure analyses revealed cubic crystal symmetry (I-43m, a = 31-36 Å) with a 3D pore system of significant void space (73-81%). The pore system features three types of pores being systematically tunable in size ranging from 17.4 to 18.8 Å (pore I), 8.2 to 12.8 Å (pore II), and 4.8 to 10.4 Å (pore III) by the choice of auxiliary ligands. All members of this series have noninterpenetrating structures and exhibit robust architectures, as evidenced by their permanent porosity and high thermal stability (up to 300 °C). The structural integrity and specific surface areas could be systematically optimized using supercritical CO2 exchange methods for framework activation resulting in BET surface areas ranging from 1250 to 2250 m2/g. Most interestingly, as a structural landmark, we found the pore surfaces lined with charge gradients employed by the pyridinium ligands. This key feature results in significant adsorption of carbon dioxide and methane which is attributed to polarization effects. With this contribution we pioneer the reticulation of pyridinium building blocks into extended zwitterionic networks in which specific properties can be targeted

Role of plant relatedness in plant–soil feedback dynamics of sympatric Asclepias species

Plants affect associated biotic and abiotic edaphic factors, with reciprocal feedbacks from soil characteristics affecting plants. These two-way interactions between plants and soils are collectively known as plant–soil feedbacks (PSFs). The role of phylogenetic relatedness and evolutionary histories have recently emerged as a potential driver of PSFs, although the strength and direction of feedbacks among sympatric congeners are not well-understood. We examined plant–soil feedback responses of Asclepias syriaca, a common clonal milkweed species, with several sympatric congeners across a gradient of increasing phylogenetic distances (A. tuberosa, A. viridis, A. sullivantii, and A. verticillata, respectively). Plant–soil feedbacks were measured through productivity and colonization by arbuscular mycorrhizal (AM) fungi. Asclepias syriaca produced less biomass in soils conditioned by the most phylogenetically distant species (A. verticillata), relative to conspecific-conditioned soils. Similarly, arbuscular mycorrhizal (AM) fungal colonization of A. syriaca roots was reduced when grown in soils conditioned by A. verticillata, compared with colonization in plants grown in soil conditioned by any of the other three Asclepias species, indicating mycorrhizal associations are a potential mechanism of observed positive PSFs. This display of differences between the most phylogenetically distant, but not close or intermediate, paring(s) suggests a potential phylogenetic threshold, although other exogenous factors cannot be ruled out. Overall, these results highlight the potential role of phylogenetic distance in influencing positive PSFs through mutualists. The role of phylogenetic relatedness and evolutionary histories have recently emerged as a potential driver of plant–soil feedbacks (PSFs), although the strength and direction of feedbacks among sympatric congeners are not well-understood. Congeneric, sympatric milkweeds typically generated positive PSFs in terms of productivity and AM fungal colonization, suggesting the low likelihood of coexistence among tested pairs, with a strength of feedback increasing as the phylogenetic distance increases

Differential processing of risk and reward in delinquent and non-delinquent youth

The present study examined the behavioral and neural differences in risky decision-making between delinquent (n = 23) and non-delinquent (n = 27) youth ages 13-17 years (M = 16, SD = 0.97) in relation to reward processing. While undergoing functional neuroimaging, participants completed an experimental risk task wherein they received feedback about the riskiness of their behavior in the form of facial expressions that morphed from happy to angry. Behavioral results indicated that delinquent youth took fewer risks and earned fewer rewards on the task than non-delinquent youth. Results from whole-brain analyses indicated no group differences in sensitivity to punishments (i.e. angry faces), but instead showed that delinquent youth evinced greater neural tracking of reward outcomes (i.e. cash-ins) in regions including the ventral striatum and inferior frontal gyrus. While behavioral results show that delinquent youth were more risk-averse, the neural results indicated that delinquent youth were also more reward-driven, potentially suggesting a preference for immediate rewards. Results offer important insights into differential decision-making processes between delinquent and non-delinquent youth

Climate Affects Plant-Soil Feedback of Native and Invasive Grasses: Negative Feedbacks in Stable but Not in Variable Environments

This work is licensed under a Creative Commons Attribution 4.0 International License.The plant-soil feedback framework allows researchers to target the interaction of plants and root-associated microbes and to determine its interplay on plant-plant interactions. Plant-soil feedbacks in terrestrial ecology are well-documented, but the strength and direction of feedbacks as influenced by abiotic environmental factors, such as temperature and soil moisture, has not been fully explored. In our study, we examined plant-soil feedback responses of both cool- and warm-season native and non-native grasses to elevated temperatures (ambient and +5°C) and soil moisture (100 and 75% field capacity). In a previous experiment, grasses were grown under temperature and soil moisture conditions similar to our current study. The resultant trained soil communities served as the inoculum sources for our current experiment. We found that consistent training and experimental temperatures resulted in negative PSF, where plants produced greater biomass in soils conditioned by heterospecifics. However, the direction of PSF was reversed when training and experimental conditions were mismatched. That is, when training and experimental temperatures mirrored one another, negative PSF occurred, suggesting coexistence between the two species is likely under these conditions. However, when only training or testing temperatures were elevated, positive PSF were detected, favoring the non-native species. These alterations in plant-soil feedbacks were relatively consistent across pairings of warm- and cool-season grasses. Overall, our results indicate inconsistent year-to-year environmental conditions, such as extreme temperatures, may undermine the stabilizing forces of negative PSF and favor of non-native grasses

Arbuscular Mycorrhizal Fungi Taxa Show Variable Patterns of Micro-Scale Dispersal in Prairie Restorations

Human land use disturbance is a major contributor to the loss of natural plant communities, and this is particularly true in areas used for agriculture, such as the Midwestern tallgrass prairies of the United States. Previous work has shown that arbuscular mycorrhizal fungi (AMF) additions can increase native plant survival and success in plant community restorations, but the dispersal of AMF in these systems is poorly understood. In this study, we examined the dispersal of AMF taxa inoculated into four tallgrass prairie restorations. At each site, we inoculated native plant species with greenhouse-cultured native AMF taxa or whole soil collected from a nearby unplowed prairie. We monitored AMF dispersal, AMF biomass, plant growth, and plant community composition, at different distances from inoculation. In two sites, we assessed the role of plant hosts in dispersal, by placing known AMF hosts in a “bridge” and “island” pattern on either side of the inoculation points. We found that AMF taxa differ in their dispersal ability, with some taxa spreading to 2-m in the first year and others remaining closer to the inoculation point. We also found evidence that AMF spread altered non-inoculated neighboring plant growth and community composition in certain sites. These results represent the most comprehensive attempt to date to evaluate AMF spread

Thermochromic Metal Halide Perovskite Windows with Ideal Transition Temperatures

Urban centers across the globe are responsible for a significant fraction of energy consumption and CO2 emission. As urban centers continue to grow, the popularity of glass as cladding material in urban buildings is an alarming trend. Dynamic windows reduce heating and cooling loads in buildings by passive heating in cold seasons and mitigating solar heat gain in hot seasons. In this work, we develop a mesoscopic building energy model that demonstrates reduced building energy consumption when thermochromic windows are employed. Savings are realized across eight disparate climate zones of the United States. We use the model to determine the ideal critical transition temperature of 20 to 27.5 {\deg}C for thermochromic windows based on metal halide perovskite materials. Ideal transition temperatures are realized experimentally in composite metal halide perovskite film composed of perovskite crystals and an adjacent reservoir phase. The transition temperature is controlled by co-intercalating methanol, instead of water, with methylammonium iodide and tailoring the hydrogen-bonding chemistry of the reservoir phase. Thermochromic windows based on metal halide perovskites represent a clear opportunity to mitigate the effects of energy-hungry buildings

Clonal karyotype evolution involving ring chromosome 1 with myelodysplastic syndrome subtype RAEB-t progressing into acute leukemia

s Karyotypic evolution is a well-known phenomenon in patients with malignant hernatological disorders during disease progression. We describe a 50-year-old male patient who had originally presented with pancytopenia in October 1992. The diagnosis of a myelodysplastic syndrome (MDS) FAB subtype RAEB-t was established in April 1993 by histological bone marrow (BM) examination, and therapy with low-dose cytosine arabinoside was initiated. In a phase of partial hernatological remission, cytogenetic assessment in August 1993 revealed a ring chromosome 1 in 13 of 21 metaphases beside BM cells with normal karyotypes {[}46,XY,r(1)(p35q31)/46,XY]. One month later, the patient progressed to an acute myeloid leukemia (AML), subtype M4 with 40% BM blasts and cytogenetic examination showed clonal evolution by the appearance of additional numerical aberrations in addition to the ring chromosome{[}46,XY,r(1),+8,-21/45,XY,r(1),+8,-21,-22/46, XY]. Intensive chemotherapy and radiotherapy was applied to induce remission in preparation for allogeneic bone marrow transplantation (BMT) from the patient's HLA-compatible son. After BMT, complete remission was clinically, hematologically and cytogenetically (normal male karyotype) confirmed. A complete hematopoietic chimerism was demonstrated. A relapse in January 1997 was successfully treated using donor lymphocyte infusion and donor peripheral blood stem cells (PB-SC) in combination with GM-CSF as immunostimulating agent in April 1997, and the patient's clinical condition remained stable as of January 2005. This is an interesting case of a patient with AML secondary to MDS. With the ring chromosome 1 we also describe a rare cytogenetic abnormality that predicted the poor prognosis of the patient, but the patient could be cured by adoptive immunotherapy and the application of donor's PB-SC. This case confirms the value of cytogenetic analysis in characterizing the malignant clone in hernatological neoplasias, the importance of controlling the quality of an induced remission and of the detection of a progress of the disease. Copyright (c) 2006 S. Karger AG, Basel

Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case–control study

We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. We conducted a population-based case–control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk

Efficacy and safety of bempedoic acid in patients not receiving statins in phase 3 clinical trials

BACKGROUND: Despite the high incidence of patients with statin tolerance problems, randomized evaluations of nonstatin oral treatment options for lowering of low-density lipoprotein cholesterol (LDL-C) in this population are sparse. OBJECTIVE: To assess the LDL-C lowering effect of bempedoic acid in patients not taking statins. METHODS: This was a pooled analysis of data from patients enrolled in four phase 3 bempedoic acid studies (12 to 52 weeks in duration) who were not taking concomitant statins (Phase 3 No Statin Cohort) and a phase 3 bempedoic acid plus ezetimibe fixed-dose combination study (BA+EZE FDC No Statin Cohort). The primary endpoint for all studies was the percent change from baseline to week 12 in LDL-C levels. Safety and tolerability were assessed by laboratory values and adverse events. RESULTS: In the Phase 3 No Statin Cohort, bempedoic acid (n = 394) lowered LDL-C levels at week 12 significantly more than placebo (n = 192; -26.5% [95% CI, -29.7%, -23.2%]; P\u3c0.001). The fixed-dose combination of bempedoic acid with ezetimibe lowered LDL-C by 39.2% (95% CI, -51.7% to -26.7%; P\u3c0.001). Muscle-related disorders occurred at a rate of 26.4 and 28.6 per 100 person-years with bempedoic acid and placebo, respectively. CONCLUSIONS: In patients with hypercholesterolemia unable to take statins, bempedoic acid lowered LDL-C levels by a mean of 26.5% vs placebo and bempedoic acid + ezetimibe fixed-dose combination lowered LDL-C by 39.2%. The treatments were generally well tolerated, suggesting that bempedoic acid may be efficacious and well tolerated in this challenging-to-treat patient population