Distributions and determinants of urinary biomarkers of organophosphate pesticide exposure in a prospective Spanish birth cohort study

Background: Prenatal exposure to organophosphate pesticides (OPs) has been associated with impaired child development. Pesticide exposure determinants need to be studied in order to identify sources and pathways of pesticide exposure. The aim of this paper is to describe prenatal exposure to OPs and evaluate the associated factors in pregnant women. Methods: The study population consisted of pregnant women ( n = 573) who participated in the INMA birth cohort study in Valencia (Spain, 2003 – 2006). OP metabolites were analyzed in maternal urine at the 32nd week of gestation using a liquid chromatography-high resolution mass spectrometry method. The analysis included non-specific (diethyl phosphate [DEP], diethyl thiophosphate [DETP], dimethyl thiophosphate [DMTP], dimethyl dithiophosphate [DMDTP]) and specific metabolites (2-diethylamino-6-methyl-4-pyrimidinol [DEAMPY], 2-isopropyl-4-methyl-6-hydroxypyrimidine [IMPY], para-nitrophenol [PNP], and 3,5,6-trichloro-2-pyridinol [TCPY]). Information about the sociodemographic, environmental, and dietary characteristics was obtained by questionnaire. The association between log-transformed OPs and covariates was analyzed using multivariable interval censored regression. Results: The detection frequencies were low, DMTP and TCPY being the most frequently detected metabolites (53.8% and 39.1%, respectively). All the OP metabolites were positive ly associated with maternal intake of fruits and vegetables. Other maternal characteristics related to the OPs were body mass index (BMI) before pregnancy and smoking habit during pregnancy. Women with lower BMI and those who did not smoke presented higher OP concentrations. Moreover, mothers who had a yard or garden with plants at home or who lived in an urban area were also more exposed to OPs. Conclusions: The OP detection frequencies and the concentrations observed in our study population were low, compared with most of the previously published studies. Given the high vulnerability of the fet us to neurotoxicant exposure, further research on the determinants of the body burdenofOPsduringpregnancywouldbenecessary.The knowledge gained from such studies would enhance the effectiveness of public health control and future recommendations in order to reduce the risk to both the health of pregnant women and the health and development of their children.his study was supported by grants from the Instituto de Salud Carlos III [FIS- FEDER 13/1944, 13/2032, 14/0891, 14/1687, 16/1288 and Miguel Servet-FEDER CP15/0025]; Conselleria de Sanitat, Generalitat Valenciana (FISABIO UGP 15 – 230) and EU (FP7-ENV-2011 DENAMIC cod 282,957

In vitro Natural Killer Cell Immunotherapy for Medulloblastoma

How the immune system attacks medulloblastoma (MB) tumors effectively is unclear, although natural killer (NK) cells play an important role in immune defense against tumor cells. Interactions between receptors on NK cells and ligands expressed by tumor cells are critical for tumor control by immunotherapy. In this study, we analyzed tumor samples from 54 MB patients for expression of major histocompatibility complex class I-related chains A (MICA) and UL16 binding protein (ULPB-2), which are ligands for the NK group 2 member D activatory receptor (NKG2D). The percentage of MICA and ULBP-2 positive cells was higher than 25% in 68% and 6% of MB patients, respectively. A moderate-high intensity of MICA cytoplasmic staining was observed in 46% MB patients and weak ULBP-2 staining was observed in 8% MB patients. No correlation between MICA/ULBP-2 expression and patient outcome was found. We observed that HTB-186, a MB cell line, was moderately resistant to NK cell cytotoxicity in vitro. Blocking MICA/ULBP-2 on HTB-186, and NKG2D receptor on NK cells increased resistance to NK cell lysis in vitro. However, HLA class I blocking on HTB-186 and overnight incubation with IL-15 stimulated NK cells efficiently killed tumor cells in vitro. We conclude that although NKG2D/MICA-ULBP-2 interactions have a role in NK cell cytotoxicity against MB, high expression of HLA class I can protect MB from NK cell cytotoxicity. Even so, our in vitro data indicate that if NK cells are appropriately stimulated, they may have the potential to target MB in vivo

Integrating Sequence Capture and Restriction Site-Associated DNA Sequencing to Resolve Recent Radiations of Pelagic Seabirds

The diversification of modern birds has been shaped by a number of radiations. Rapid diversification events make reconstructing the evolutionary relationships among taxa challenging due to the convoluted effects of incomplete lineage sorting (ILS) and introgression. Phylogenomic data sets have the potential to detect patterns of phylogenetic incongruence, and to address their causes. However, the footprints of ILS and introgression on sequence data can vary between different phylogenomic markers at different phylogenetic scales depending on factors such as their evolutionary rates or their selection pressures. We show that combining phylogenomic markers that evolve at different rates, such as paired-end double-digest restriction site-associated DNA (PE-ddRAD) and ultraconserved elements (UCEs), allows a comprehensive exploration of the causes of phylogenetic discordance associated with short internodes at different timescales. We used thousands of UCE and PE-ddRAD markers to produce the first well-resolved phylogeny of shearwaters, a group of medium-sized pelagic seabirds that are among the most phylogenetically controversial and endangered bird groups. We found that phylogenomic conflict was mainly derived from high levels of ILS due to rapid speciation events. We also documented a case of introgression, despite the high philopatry of shearwaters to their breeding sites, which typically limits gene flow. We integrated state- of-the-art concatenated and coalescent-based approaches to expand on previous comparisons of UCE and RAD-Seq data sets for phylogenetics, divergence time estimation, and inference of introgression, and we propose a strategy to optimize RAD-Seq data for phylogenetic analyses. Our results highlight the usefulness of combining phylogenomic markers evolving at different rates to understand the causes of phylogenetic discordance at different timescales.

Palaeoceanographic changes in the late Pliocene promoted rapid diversification in pelagic seabirds

Aim: Palaeoceanographic changes can act as drivers of diversification and speciation, even in highly mobile marine organisms. Shearwaters are a group of globally distributed and highly mobile pelagic seabirds. Despite a recent well-resolved phylogeny, shearwaters have controversial species limits, and show periods of both slow and rapid diversification. Here, we explore the role of palaeoceanographic changes on shearwaters' diversification and speciation. We investigate shearwater biogeography and the evolution of a key phenotypic trait, body size, and we assess the validity of their current taxonomy

Remanence enhancement for stray field-based applications in arrays of crystalline nanomagnets

With the aim of achieving stable, substantial remanences adequate for exploitation in stray field-based applications, we report on the hysteresis behavior occurring in arrays of single-crystal Fe motifs, a-beam lithographed into prisms with triangular bases and different orientations of their magnetocrystalline axes with respect to the morphological symmetry axes. From both experimental and simulational analyses we recognize the fact that the magnetization reversal processes of our samples were mediated by motif-sized vortices. Their nucleation and annihilation fields and sites within the motifs, and their field-induced displacements, are discussed in terms of the magnetocrystalline and configurational anisotropies and inter-motif dipolar interactions. From our data, we conclude that reduced remanences as large as 0.85 (sufficient for the application requirements), protected by nucleation fields of several tens of Oe, can be produced in arrays where magnetocrystalline easy axes reinforce and partly compensate the easiest and hardest configurational ones, respectively. The angular dependence of the reduced remanence associated with interplay of these anisotropies corresponds to a symmetry reduction from the triaxial one linked to the triangular morphology down to an effective uniaxial one. We also identify, for the particular case of inter-nanoprism distances that are short in comparison with the dimensions of the motif base, a contribution to the remanence enhancement originating from the dipolar interactions

Adverse events related to central venous catheters (CVC) and the influence of CVC characteristics on peripheral blood hematopoietic progenitor cell collection in children

Introduction: The use of peripheral blood progenitor cells (PBPCs) as a source for hematopoietic stem cell transplantation (HSCT) in pediatric healthy donors is still under debate. The risk of a central venous catheter (CVC) placement and catheter-related complications continue to be the main arguments to discourage its use. Methods: we present a retrospective analysis of 140 PBPC collections in pediatric patients and donors, describing adverse events (AE) related to CVCs as well as the influence of catheterrelated variables on the efficiency of the leukapheresis. Results: 14 CVC-related AEs were recorded (10%). The most common was fever in 5 patients, 4 of which had a catheter-related bacteriemia. Thrombotic events were only observed in 3 patients with active malignancy. A healthy donor presented a moderate bleeding after catheter withdrawal that resolved with local measures, and none of the rest presented any AE. Regarding variables related to the development of AEs, the subject group (patient or donor) was the only one significantly associated (p < 0.0001). Of interest, efficiency was also related to catheter location, being worse in those located in the femoral vein than in into the jugular or the subclavian veins (p < 0.05). In a multivariate analysis, the only variable significantly associated was catheter size (beta 0.238, p < 0.01). Discussion: Placing a CVC for PBPC collection in pediatric subjects is overall safe; CVC-related complications in pediatric healthy donors are very rare. Furthermore, we should try to place catheters of the largest caliber possible, since the efficiency of the collection is related to this variabl

On the applicability of ray-tracing propagation models to V2V-intersection environments

In this work, we analyze the applicability of a geometric-based stochastic (GBS) model based on ray-tracing techniques to vehicular-to-vehicular (V2V) intersections. The accuracy and usefulness of the proposed model is analyzed using simulated results and narrowband channel measurements at 5.9 GHz. The results show that these type of models can be a good choice to evaluate communications protocols and system performance of future vehicular networks

Identification of a novel modulator of thyroid hormone receptor-mediated action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease

Identification of a Novel Modulator of Thyroid Hormone Receptor-Mediated Action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease

Millimeter-wave channel measurements and path loss characterization in a typical indoor office environment

In this paper, a path loss characterization at millimeter-wave (mmWave) frequencies is performed in a typical indoor office environment. Path loss results were derived from propagation channel measurements collected in the 25–40 GHz frequency band, in both line-of-sight (LOS) and obstructed-LOS (OLOS) propagation conditions. The channel measurements were performed using a frequency-domain channel sounder, which integrates an amplified radio over fiber (RoF) link to avoid the high losses at mmWave. The path loss was analyzed in the 26 GHz, 28 GHz, 33 GHz and 38 GHz frequency bands through the close-in free space reference distance (CI) and the floating-intercept (FI) models. These models take into account the distance dependence of the path loss for a single frequency. Nevertheless, to jointly study the distance and frequency dependence of the path loss, multi-frequency models were considered. The parameters of the ABG (A-alpha, B-beta and G-gamma) and the close-in free space reference distance with frequency path loss exponent (CIF) models were derived from the channel measurements in the whole 25–40 GHz band under the minimum mean square error (MMSE) approach. The results show that, in general, there is some relationship between the model parameters and the frequency. Path loss exponent (PLE) values smaller than the theoretical free space propagation were obtained, showing that there are a waveguide effect and a constructive interference of multipath components (MPCs). Since the measurements were obtained in the same environment and with the same configuration and measurement setup, it is possible to establish realistic comparisons between the model parameters and the propagation behavior at the different frequencies considered. The results provided here allow us to have a better knowledge of the propagation at mmWave frequencies and may be of interest to other researchers in the simulation and performance evaluation of future wireless communication systems in indoor hotspot environments.This work has been funded in part by the MCIN/AEI/10.13039/501100011033/ through the I+D+i Project under Grant PID2020-119173RB-C21 and Grant PID2020-119173RB-C22, and by COLCIENCIAS in Colombia