A hyperactive quantitative trait locus allele of Arabidopsis BRX contributes to natural variation in root growth vigor.

Quantitative trait loci analysis of natural Arabidopsis thaliana accessions is increasingly exploited for gene isolation. However, to date this has mostly revealed deleterious mutations. Among them, a loss-of-function allele identified the root growth regulator BREVIS RADIX (BRX). Here we present evidence that BRX and the paralogous BRX-LIKE (BRXL) genes are under selective constraint in monocotyledons as well as dicotyledons. Unexpectedly, however, whereas none of the Arabidopsis orthologs except AtBRXL1 could complement brx null mutants when expressed constitutively, nearly all monocotyledon BRXLs tested could. Thus, BRXL proteins seem to be more diversified in dicotyledons than in monocotyledons. This functional diversification was correlated with accelerated rates of sequence divergence in the N-terminal regions. Population genetic analyses of 30 haplotypes are suggestive of an adaptive role of AtBRX and AtBRXL1. In two accessions, Lc-0 and Lov-5, seven amino acids are deleted in the variable region between the highly conserved C-terminal, so-called BRX domains. Genotyping of 42 additional accessions also found this deletion in Kz-1, Pu2-7, and Ws-0. In segregating recombinant inbred lines, the Lc-0 allele (AtBRX(Lc-0)) conferred significantly enhanced root growth. Moreover, when constitutively expressed in the same regulatory context, AtBRX(Lc-0) complemented brx mutants more efficiently than an allele without deletion. The same was observed for AtBRXL1, which compared with AtBRX carries a 13 amino acid deletion that encompasses the deletion found in AtBRX(Lc-0). Thus, the AtBRX(Lc-0) allele seems to contribute to natural variation in root growth vigor and provides a rare example of an experimentally confirmed, hyperactive allelic variant.

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Influence of Assisted Reproductive Techniques in the occurrence of weight discordance in twin gestations

Background:There is no actual evidence that the ART are directly related to the occurrence of weight discordance. In some studies, ART-­‐conceived twin pregnancies are at greater risk than non-­‐ART-­‐conceived ones for pregnancy complications and adverse perinatal outcome: the incidences of pregnancy-­‐induced hypertension, uterine bleeding, premature contractions, IUGR, fetal death, discordance, and cesarean section were significantly higher. Discordance rate was elevated (25.3% vs.17.0%) among ART twins, which can increase perinatal risk (increased incidence of SGA and NICU admission). Other studies say that perinatal and neonatal morbidity, gestational age at delivery, and birth weight are not affected by ART. Regarding the first trimester ultrasound, some studies didn’t notice significant differences in CRL disparity or birth weight discordance between spontaneous and ART-­‐ conceived dichorionic twin pregnancies. In ART-­‐conceived dichorionic twin pregnancies, CRL disparity may be associated with birth weight discordance. In some studies, CRL discordance in twin pregnancies in the first trimester was a frequent finding. Objectives: To analyze the association of the ART in the occurrence of weight discordance in the pregnancies between 2010 and 2013 in the Hospital Universitari de Girona Doctor Josep Trueta, and to describe the proportion of diagnosis of growth discordance in the first trimester by the ultrasonography technology. Methods: A retrospective cohort study will be performed in those patients with twin pregnancies between 2010 and 2013, within the Hospital Universitari de Girona Doctor Josep Trueta (HUJT). A retrospective and descriptive study will be done in those cases with discordance weight in the moment of the birth, in which the CRL will be studied in the first trimester ultrasound, describing the percentage of discordance detected in that moment. The general characteristics of the sample are going to be analyzed by Logistic RegressionInfluenceof

Crosstalk of Notch with p53 and p63 in cancer growth control.

Understanding the complexity of cancer depends on an elucidation of the underlying regulatory networks, at the cellular and intercellular levels and in their temporal dimension. This Opinion article focuses on the multilevel crosstalk between the Notch pathway and the p53 and p63 pathways. These two coordinated signalling modules are at the interface of external damaging signals and control of stem cell potential and differentiation. Positive or negative reciprocal regulation of the two pathways can vary with cell type and cancer stage. Therefore, selective or combined targeting of the two pathways could improve the efficacy and reduce the toxicity of cancer therapies.

Growth and functionalization of carbon nanotubes on quartz filter for environmental applications

Background: Air pollution has become an important issue worldwide due to its adverse health effects. Among the different air contaminants, volatile organic compounds (VOCs) are liquids or solids with a high vapor pressure at room temperature that are extremely dangerous for human health. Removal of these compounds can be achieved using nanomaterials with tailored properties such as carbon nanotubes. Methods: Vertically-aligned multiwall carbon nanotubes (CNTs) were successfully grown on quartz filters by means of plasma enhanced chemical vapor deposition (PECVD). Furthermore, a plasma treatment was performed in order to modify the surface properties of the CNTs. The adsorption/desorption processes of three chlorinated compounds (trichloroethylene, 1,2-dichlorobenzene and chloroform) on the CNTs were studied using mass spectrometry measurements with a residual gas analyzer. Results: The adsorption capability of the CNTs increased after functionalization of their surface with a water plasma treatment. In addition, it was found that the presence of aromatic rings, water solubility and polarity of the VOCs play an important role on the adsorption/desorption kinetics at the CNTs surface. Conclusions: This study demonstrates the applicability of CNTs deposited on quartz filters for the removal or selective detection of volatile organic compounds (VOCs). The presence of aromatic rings in VOCs results in π -stacking interactions with a significant increase of their adsorption. On the other hand, it was found that CNTs surface interactions increase with water solubility and polarity of the VOC.

The effects of selective estrogen receptor modulators on the death of breast cancer cells and osteoblastic cells

Selektiivisten estrogeenireseptorin muuntelijoiden (serm) vaikutus rintasyöpäsolujen ja luun solujen kuolemaan Selektiiviset estrogeenireseptorin muuntelijat (SERMit) ovat ryhmä kemialliselta rakenteeltaan erilaisia yhdisteitä jotka sitoutuvat solunsisäisiin estrogeenireseptoreihin toimien joko estrogeenin kaltaisina yhdisteinä tai estrogeenin vastavaikuttajina. Tamoksifeeni on SERM –yhdiste, jota on jo pitkään käytetty estrogeenireseptoreita (ER) ilmentävän rintasyövän lääkehoidossa. Tamoksifeeni sekä estää rintasyöpäsolujen jakaantumista että toisaalta aikaansaa niiden apoptoosin eli ohjelmoidun solukuoleman muuntelemalla ER-välitteisesti kohdesolun geenien ilmentymistä. Viimeaikaiset tutkimustulokset ovat kuitenkin osoittaneet tamoksifeenilla olevan myös nopeampia, nongenomisia vaikutusmekanismeja. Tässä väitöskirjatyössä tutkimme niitä nopeita vaikutusmekanismeja joiden avulla tamoksifeeni vaikuttaa rintasyöpäsolujen elinkykyyn. Osoitamme että tamoksifeeni farmakologisina pitoisuuksina aikaansaa nopean mitokondriaalisen solukuolemaan johtavan signallointireitin aktivoitumisen rintasyöpäsoluissa. Tämän lisäksi tutkimme myös tamoksifeenin aiheuttamaan mitokondriovaurioon johtavia tekijöitä. Tutkimustuloksemme osoittavat että ER-positiivisissa rintasyöpäsoluissa tamoksifeeni indusoi pitkäkestoisen ERK-kinaasiaktivaation, joka voidaan estää 17-beta-estradiolilla. Tamoksifeenin aikaansaama nopea solukuolema on pääosin ER:sta riippumaton tapahtuma, mutta siihen voidaan vaikuttaa myös ER-välitteisin mekanismein. Sen sijaan epidermaalisen kasvutekijäreseptorin (EGFR) voitiin osoittaa osallistuvan tamoksifeenin nopeiden vaikutusten välittämiseen. Tämän lisäksi vertailimme myös estradiolin ja eri SERM-yhdisteiden kykyä suojata apoptoosilta käyttämällä osteoblastiperäisiä soluja. Pytyäksemme vertailemaan ER-isotyyppien roolia eri yhdisteiden suojavaikutuksissa, transfektoimme U2OS osteosarkoomasolulinjan ilmentämään pysyvästi joko ERalfaa tai ERbetaa. Tulostemme mukaan sekä estradioli että uusi SERM-yhdiste ospemifeeni suojaavat osteoblastin kaltaisia soluja etoposidi-indusoidulta apoptoosilta. Sekä ERalfa että ERbeta pystyivät välittämään suojavaikutusta, joskin vaikutukset erosivat toisistaan. Lisäksi havaitsimme edellä mainitun suojavaikutuksen olevan yhteydessä muutoksiin solujen sytokiiniekspressiossa. Tietoa SERM-yhdisteiden anti-ja proapoptoottisten vaikutusmekanismeista eri kohdekudoksissa voidaan mahdollisesti hyödyntää kehiteltäessä uusia kudosspesifisiä SERM-yhdisteitä.

Calcium-Mediated Induction of Paradoxical Growth following Caspofungin Treatment Is Associated with Calcineurin Activation and Phosphorylation in Aspergillus fumigatus.

The echinocandin antifungal drug caspofungin at high concentrations reverses the growth inhibition of Aspergillus fumigatus, a phenomenon known as the "paradoxical effect," which is not consistently observed with other echinocandins (micafungin and anidulafungin). Previous studies of A. fumigatus revealed the loss of the paradoxical effect following pharmacological or genetic inhibition of calcineurin, yet the underlying mechanism is poorly understood. Here, we utilized a codon-optimized bioluminescent Ca(2+) reporter aequorin expression system in A. fumigatus and showed that caspofungin elicits a transient increase in cytosolic free Ca(2+) ([Ca(2+)]c) in the fungus that acts as the initial trigger of the paradoxical effect by activating calmodulin-calcineurin signaling. While the increase in [Ca(2+)]c was also observed upon treatment with micafungin, another echinocandin without the paradoxical effect, a higher [Ca(2+)]c increase was noted with the paradoxical-growth concentration of caspofungin. Treatments with a Ca(2+)-selective chelator, BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid], or the L-type Ca(2+) channel blocker verapamil abolished caspofungin-mediated paradoxical growth in both the wild-type and the echinocandin-resistant (EMFR-S678P) strains. Concomitant with increased [Ca(2+)]c levels at higher concentrations of caspofungin, calmodulin and calcineurin gene expression was enhanced. Phosphoproteomic analysis revealed that calcineurin is activated through phosphorylation at its serine-proline-rich region (SPRR), a domain previously shown to be essential for regulation of hyphal growth, only at a paradoxical-growth concentration of caspofungin. Our results indicate that as opposed to micafungin, the increased [Ca(2+)]c at high concentrations of caspofungin activates calmodulin-calcineurin signaling at both a transcriptional and a posttranslational level and ultimately leads to paradoxical fungal growth.

Cross-country data on the quantity of schooling: a selective survey and some quality measures

We survey a number of papers that have focused on the construction of cross-country data sets on average years of schooling. We discuss the construction of the different series, compare their profiles and construct indicators of their information content. The discussion focuses on a sample of OECD countries but we also provide some results for a large non-OECD sample.

Semi-selective medium for Fusarium graminearum detection in seed samples

Fungi of the genus Fusarium cause a variety of difficult to control diseases in different crops, including winter cereals and maize. Among the species of this genus Fusarium graminearum deserves attention. The aim of this work was to develop a semi-selective medium to study this fungus. In several experiments, substrates for fungal growth were tested, including fungicides and antibiotics such as iprodiona, nystatin and triadimenol, and the antibacterial agents streptomycin and neomycin sulfate. Five seed samples of wheat, barley, oat, black beans and soybeans for F. graminearum detection by using the media Nash and Snyder agar (NSA), Segalin & Reis agar (SRA) and one-quarter dextrose agar (1/4PDA; potato 50g; dextrose 5g and agar 20g), either unsupplemented or supplemented with various concentrations of the antimicrobial agents cited above. The selected components and concentrations (g.L-1) of the proposed medium, Segalin & Reis agar (SRA-FG), were: iprodiona 0.05; nystatin 0,025; triadimenol 0.015; neomycin sulfate 0.05; and streptomycin sulfate, 0.3 added of ¼ potato sucrose agar. In the isolation from seeds of cited plant species, the sensitivity of this medium was similar to that of NSA but with de advantage of maintaining the colony morphological aspects similar to those observed in potato-dextrose-agar medium.

Effect of selectivity of herbicides and plant growth regulators used in sugarcane crops on immature stages of Trichogramma galloi (Hymenoptera: Trichogrammatidae)

Herbicides and plant growth regulators are often used in sugarcane management. However, the use of non-selective pesticides can cause adverse effects on the efficiency of beneficial insects in integrated pest management. Within this context, this study aimed to evaluate the effect of such products on the immature stages of the parasitoid Trichogramma galloi. Eggs of Diatraea saccharalis containing the parasitoid at the egg-larva stage and at the prepupal and pupal stages were immersed in test solutions of the following pesticides (maximum recommended doses for sugarcane): herbicides clomazone and diuron + hexazinone, and plant growth regulators trinexapac-ethyl and sulfometuron-methyl. The biological properties evaluated were emergence (F1 and F2) and number of eggs parasitized by T. galloi (F1). The products were classified according to percentage of reduction in emergence and parasitism: harmless (<30%), slightly harmful (30-79%), moderately harmful (80-99%) and harmful (>99%). The pesticides evaluated were considered to be harmless or slightly harmful to immature T. galloi and, thus, their use should be preferred for preserving this parasitoid species in sugarcane management programs.

Increase in skeletal muscle protein content by the ß-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet

This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the ß-2 selective agonist clenbuterol (CL). Males (4 weeks old) from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group). CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks) caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A), were further reduced in CL rats (A = 25.05 ± 0.31 vs CL = 23.64 ± 0.30 g/l, P<0.05). Total liver protein decreased below the level seen in either pair-fed animals (group P) or animals with free access to the low-protein diet (A = 736.56 ± 26 vs CL = 535.41 ± 54 mg, P<0.05), whereas gastrocnemius muscle protein was higher than the values normally described for control (C) animals (C = 210.88 ± 3.2 vs CL = 227.14 ± 1.7 mg/g, P<0.05). Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 ± 1.1 vs CL = -10.2 ± 1.9 g, P<0.05). This was associated with a marked decrease in fat stores (P = 5.35 ± 0.81 vs CL = 2.02 ± 0.16 g, P<0.05). Brown adipose tissue (BAT) cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 ± 16.20 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05), was still much higher than in control rats (C = 159.55 ± 11.54 vs CL = 414.48 ± 11.32 U/BAT x kg body weight, P<0.05). The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.

Reduction of intraspecific aggression in adult rats by neonatal treatment with a selective serotonin reuptake inhibitor

Most studies suggest that serotonin exerts an inhibitory control on the aggression process. According to experimental evidence, this amine also influences growth and development of the nervous tissue including serotoninergic neurons. Thus, the possibility exists that increased serotonin availability in young animals facilitates a long-lasting effect on aggressive responses. The present study aimed to investigate the aggressive behavior of adult rats (90-120 days) treated from the 1st to the 19th postnatal day with citalopram (CIT), a selective serotonin reuptake inhibitor (20 mg/kg, sc, every 3 days). Aggressive behavior was induced by placing a pair of rats (matched by weight) in a box (20 x 20 x 20 cm), and submitting them to a 20-min session of electric footshocks (five 1.6-mA - 2-s current pulses, separated by a 4-min intershock interval). When compared to the control group (rats treated for the same period with equivalent volumes of saline solution), the CIT group presented a 41.4% reduction in the duration of aggressive response. The results indicate that the repeated administration of CIT early in life reduces the aggressive behavior in adulthood and suggest that the increased brain serotoninergic activity could play a role in this effect.

Normal skin and hypertrophic scar fibroblasts differentially regulate collagen and fibronectin expression as well as mitochondrial membrane potential in response to basic fibroblast growth factor

Basic fibroblast growth factor (bFGF) regulates skin wound healing; however, the underlying mechanism remains to be defined. In the present study, we determined the effects of bFGF on the regulation of cell growth as well as collagen and fibronectin expression in fibroblasts from normal human skin and from hypertrophic scars. We then explored the involvement of mitochondria in mediating bFGF-inducedeffects on the fibroblasts. We isolated and cultivated normal and hypertrophic scar fibroblasts from tissue biopsies of patients who underwent plastic surgery for repairing hypertrophic scars. The fibroblasts were then treated with different concentrations of bFGF (ranging from 0.1 to 1000 ng/mL). The growth of hypertrophic scar fibroblasts became slower with selective inhibition of type I collagen production after exposure to bFGF. However, type III collagen expression was affected in both normal and hypertrophic scar fibroblasts. Moreover, fibronectin expression in the normal fibroblasts was up-regulated after bFGF treatment. bFGF (1000 ng/mL) also induced mitochondrial depolarization in hypertrophic scar fibroblasts (P < 0.01). The cellular ATP level decreased in hypertrophic scar fibroblasts (P < 0.05), while it increased in the normal fibroblasts following treatment with bFGF (P < 0.01). These data suggest that bFGF has differential effects and mechanisms on fibroblasts of the normal skin and hypertrophic scars, indicating that bFGF may play a role in the early phase of skin wound healing and post-burn scar formation.

Cell cycle synchronization and BrdU incorporation as a tool to study the possible selective elimination of ErbB1 gene in the micronuclei in A549 cells

Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene that encodes epidermal growth factor receptor (EGFR). ErbB1 amplification and mutation are associated with tumor aggressiveness and low response to therapy. The aim of the present study was to design a schedule to synchronize the cell cycle of A549 cell line (a non-small cell lung cancer) and to analyze the possible association between the micronuclei (MNs) and the extrusion of ErbB1 gene extra-copies. After double blocking, by the process of fetal bovine serum deprivation and vincristine treatment, MNs formation was monitored with 5-bromo-2-deoxyuridine (BrdU) incorporation, which is an S-phase marker. Statistical analyses allowed us to infer that MNs may arise both in mitosis as well as in interphase. The MNs were able to replicate their DNA and this process seemed to be non-synchronous with the main cell nuclei. The presence of ErbB1 gene in the MNs was evaluated by fluorescent in situ hybridization (FISH). ErbB1 sequences were detected in the MNs, but a relation between the MNs formation and extrusion of amplified ErbB1could not be established. The present study sought to elucidate the meaning of MNs formation and its association with the elimination of oncogenes or other amplified sequences from the tumor cells.