We study the light and heavy quark mass dependence of the low-lying charmed mesons in the framework of one-loop HHχPT. The low energy constants are determined by analyzing the available lattice data ...from different LQCD simulations. Model selection tools are implemented to determine the relevant parameters as required by data with a higher precision. Discretization and other effects due to the charm quark mass setting are discussed.
Pesticides can interact with each other in various ways according to the compound itself and its chemical family, the dose and the targeted organs, leading to various effects. The term interaction ...means situations where some or all individual components of a mixture influence each other’s toxicity and the joint effects may deviate from the additive predictions. The various mixture effects can be greatly determined by toxicokinetic and toxicodynamic factors involving metabolic pathways and cellular or molecular targets of individual pesticides, respectively. However, the complexity of toxicological interactions can lead to unpredictable effects of pesticide mixtures. Interactions on metabolic processes affecting the biotransformation of pesticides seem to be by far the most common mechanism of synergism. Moreover, the identification of pesticides responsible for synergistic interactions is an important issue for cumulative risk assessment. Cholinesterase inhibiting insecticides (organophosphates and
N
-methylcarbamates), triazole fungicides, triazine herbicides, and pyrethroid insecticides are overrepresented in the synergistic mixtures identified so far. Since the limited available empirical evidence suggests that synergisms at dietary exposure levels are rather rare, and experimentally occurred at unrealistic high concentrations, synergism cannot be predicted quantitatively on the basis of the toxicity of mixture components. The prediction of biological responses elicited by interaction of pesticides with each other (or with other chemicals) will benefit from using a systems toxicology approach. The identification of core features of pesticide mixtures at molecular level, such as gene expression profiles, could be helpful to assess or predict the occurrence of interactive effects giving rise to unpredicted responses.
Heart failure (HF) represents the leading cause of morbidity and mortality in adult patients with congenital heart disease. The nature of underlying congenital heart disease has bearing on timing and ...severity of HF and impacts on short- and long-term outcomes. HF can be subclinical, underscoring the need for close follow-up at tertiary centres with timely management of target hemodynamic lesions. Drug therapies have an effect in systemic left ventricle failure and are employed in acute HF for symptomatic relief. Data on elective drug therapy for the failing systemic right ventricle and/or Fontan circulation is currently lacking. Drugs such as angiotensin receptor blockers with neprilysin inhibitors or sodium-glucose co-transporter-2 inhibitors may show benefit. Cardiac resynchronization therapy, in appropriately selected patients, is considered a treatment option. Mechanical circulatory support and transplantation remain the last resource in highly selected patients. As the congenital heart disease population continues to grow and age, both outpatient and inpatient service for HF will continue to play a major role in the care of adult patients with congenital heart disease.
Main illustration. Strategic overview of the management of heart failure in adult congenital heart disease; ACEI angiotensin-converting enzyme inhibitors; ARNI angiotensin receptor blockers with neprilysin inhibitors; CV cardiovascular; CRT cardiac resynchronization therapy; EF ejection fraction; ERA endothelin receptor antagonist; HF heart failure; ICD implantable cardioverter defibrillator; LBBB left bundle branch block; LV left ventricle, MCS mechanical circulatory support; MRA mineralocorticoid receptor antagonists; NYHA FC New York Heart Association functional class; PAH pulmonary arterial hypertension; PDE5I phosphodiesterase type 5 inhibitor; RV right ventricle; SR sinus rhythm. Display omitted
•Heart failure is the leading cause of morbidity and mortality in adult patients with congenital heart disease•Adult patients with congenital heart disease have approximately 25% risk of death within 1year following their first heart failure admission•Diagnosis and treatment of heart failure is challenged due to heterogeneous underlying mechanisms and should be provided in a tertiary setting
Exposure to metal(loid)s during critical developmental windows could result in permanent damage to the target organ system, increasing susceptibility to disease later in life. In view of the fact ...that metals(loid)s have been shown to work as obesogens, the aim of the present case-control study was to evaluate the modification effect of exposure to metal(loid)s on the association between SNPs in genes involved in metal(loid) detoxification and excess body weight among children. A total of 134 Spanish children aged 6–12 years old were included (88 controls and 46 cases). Seven SNPs (GSTP1 rs1695 and rs1138272; GCLM rs3789453, ATP7B rs1061472, rs732774 and rs1801243; and ABCC2 rs1885301) were genotyped on GSA microchips, and ten metal(loid)s were analysed in urine samples through Inductively coupled plasma mass spectrometry (ICP-MS). Multivariable logistic regressions were conducted to assess the genetic and metal exposures' main association and interaction effects. GSTP1 rs1695 and ATP7B rs1061472 showed significant effects on excess weight increase in those children carrying two copies of the risk G allele and being highly exposed to chromium (ORa = 5.38, p = 0.042, p interaction = 0.028 for rs1695; and ORa = 4.20, p = 0.035, p interaction = 0.012 for rs1061472) and lead (ORa = 7.18, p = 0.027, p interaction = 0.031 for rs1695, and ORa = 3.42, p = 0.062, p interaction = 0.010 for rs1061472). Conversely, GCLM rs3789453 and ATP7B rs1801243 appeared to play a protective role against excess weight in those exposed to copper (ORa = 0.20, p = 0.025, p interaction = 0.074 for rs3789453) and lead (ORa = 0.22, p = 0.092, p interaction = 0.089 for rs1801243). Our findings provide the first proof that interaction effects could exist between genetic variants within GSH and metal transporting systems and exposure to metal(loid)s, on excess body weight among Spanish children.
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•GSTP1 rs1695 and ATP7B rs1061472 contributed to excess weight in the presence of chromium and lead.•GCLM rs3789453 and ATP7B rs1801243 showed the opposite effect for copper and lead exposures.•First gene – metal(loid) interactions reported in excess body weight among children.
Summary
Rhizomania of sugar beet, caused by Beet necrotic yellow vein virus (BNYVV), is characterized by excessive lateral root (LR) formation leading to dramatic reduction of taproot weight and ...massive yield losses. LR formation represents a developmental process tightly controlled by auxin signaling through AUX/IAA‐ARF responsive module and LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcriptional network. Several LBD transcription factors play central roles in auxin‐regulated LR development and act upstream of EXPANSINS (EXPs), cell wall (CW)‐loosening proteins involved in plant development via disruption of the extracellular matrix for CW relaxation and expansion. Here, we present evidence that BNYVV hijacks these auxin‐regulated pathways resulting in formation LR and root hairs (RH). We identified an AUX/IAA protein (BvAUX28) as interacting with P25, a viral virulence factor. Mutational analysis indicated that P25 interacts with domains I and II of BvAUX28. Subcellular localization of co‐expressed P25 and BvAUX28 showed that P25 inhibits BvAUX28 nuclear localization. Moreover, root‐specific LBDs and EXPs were greatly upregulated during rhizomania development. Based on these data, we present a model in which BNYVV P25 protein mimics action of auxin by removing BvAUX28 transcriptional repressor, leading to activation of LBDs and EXPs. Thus, the evidence highlights two pathways operating in parallel and leading to uncontrolled formation of LRs and RHs, the main manifestation of the rhizomania syndrome.
BL13‐XALOC is currently the only macromolecular crystallography beamline at the 3 GeV ALBA synchrotron near Barcelona, Spain. The optics design is based on an in‐vacuum undulator, a Si(111) ...channel‐cut crystal monochromator and a pair of KB mirrors. It allows three main operation modes: a focused configuration, where both mirrors can focus the beam at the sample position to 52 µm × 5.5 µm FWHM (H × V); a defocused configuration that can match the size of the beam to the dimensions of the crystals or to focus the beam at the detector; and an unfocused configuration, where one or both mirrors are removed from the photon beam path. To achieve a uniform defocused beam, the slope errors of the mirrors were reduced down to 55 nrad RMS by employing a novel method that has been developed at the ALBA high‐accuracy metrology laboratory. Thorough commissioning with X‐ray beam and user operation has demonstrated an excellent energy and spatial stability of the beamline. The end‐station includes a high‐accuracy single‐axis diffractometer, a removable mini‐kappa stage, an automated sample‐mounting robot and a photon‐counting detector that allows shutterless operation. The positioning tables of the diffractometer and the detector are based on a novel and highly stable design. This equipment, together with the operation flexibility of the beamline, allows a large variety of types of crystals to be tackled, from medium‐sized crystals with large unit‐cell parameters to microcrystals. Several examples of data collections measured during beamline commissioning are described. The beamline started user operation on 18 July 2012.
•Few studies have examined the effects of early co-exposure to neurotoxic metals.•As, Cd, Hg, Mn and Pb placental levels were explored in relation to neurodevelopment.•Exposure to As and Hg was ...associated with cognitive impairment in preschoolers.•The effects of Cd and Mn on neurodevelopment appear to be less clear.
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We sought to determine whether prenatal co-exposure to As, Cd, Hg, Mn, and Pb was associated with impaired neurodevelopment in preschool children from the Spanish Environment and Childhood (INMA) Project, using the placenta as exposure matrix. We measured metal levels in placenta tissue samples randomly selected from five of the seven population-based birth cohorts participating in the INMA Project, collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was carried through the use of the McCarthy Scales of Children's Abilities (MSCA) at the age of 4–5years. Data on placental metal levels, MSCA scores, and relevant covariates was available for 302 children. Mn was detected in all placental samples, Cd in nearly all placentas (99%) and As, Hg, and Pb in 22%, 58%, and 17% of the placentas, respectively. After adjusting for potential confounders, detectable As levels were associated with decrements in global and verbal executive functions and quantitative abilities; detectable Hg was associated with lower scores on the verbal function of posterior cortex in a dose-response manner, and non-linearly related to poorer motor function and gross motor skills; and Mn levels were associated with decrement in perceptual-performance skills in a dose-response manner but with better memory span and quantitative skills. A synergistic interactive effect was found between As and Pb with respect to the general cognitive score, whereas an antagonistic interaction was found between Mn and Hg. Prenatal exposure to As and Hg may be a risk factor for cognitive and motor impairment in children, while the effects of Cd and Mn on neurodevelopment are less clear. Future studies should examine combined and interactive effects of exposure to multiple metals during vulnerable periods of brain development prospectively.
(BNYVV) and
(BSBMV) are closely related species, but disease development induced in their host sugar beet displays striking differences.
induces excessive lateral root (LR) formation, whereas ...BSBMV-infected roots appear asymptomatic. A comparative transcriptome analysis was performed to elucidate transcriptomic changes associated with disease development. Many differentially expressed genes (DEGs) were specific either to BNYVV or BSBMV, although both viruses shared a high number of DEGs. Auxin biosynthesis pathways displayed a stronger activation by BNYVV compared to BSBMV-infected plants. Several genes regulated by auxin signalling and required for LR formation were exclusively altered by BNYVV. Both viruses reprogrammed the transcriptional network, but a large number of transcription factors involved in plant defence were upregulated in BNYVV-infected plants. A strong activation of pathogenesis-related proteins by both viruses suggests a salicylic acid or jasmonic acid mediated-defence response, but the data also indicate that both viruses counteract the SA-mediated defence. The ethylene signal transduction pathway was strongly downregulated which probably increases the susceptibility of sugar beet to
infection. Our study provides a deeper insight into the interaction of BNYVV and BSBMV with the economically important crop sugar beet.
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