Search

The alternation of the words for "love" in John 21:15-17 is a long-standing puzzle that has defied solution. It is suggested in this note that ἀγαπῶ and φιλῶ carry a slight difference of "formality" as a result of their history and that this can account for the interplay. [ABSTRACT FROM AUTHOR]

Background: Since non-invasive prenatal testing (NIPT) in maternal blood became available, we evaluated which chromosome aberrations found in our cohort of fetuses with an enlarged NT in the first trimester of pregnancy (tested with SNP microarray) could be detected by NIPT as well. Method: 362 fetuses were referred for cytogenetic testing due to an enlarged NT (≥3.5 mm). Chromosome aberrations were investigated using QF-PCR, karyotyping and whole genome SNP array. Results: After invasive testing a chromosomal abnormality was detected in 137/362 (38 %) fetuses. 100/362 (28 %) cases concerned trisomy 21, 18 or 13, 25/362 (7 %) an aneuploidy of sex chromosomes and 3/362 (0.8 %) triploidy. In 6/362 (1.6 %) a pathogenic structural unbalanced chromosome aberration was seen and in 3/362 (0.8 %) a susceptibility locus for neurodevelopmental disorders was found. We estimated that in 2-10 % of fetuses with enlarged NT a chromosome aberration would be missed by current NIPT approaches. Conclusion: Based on our cohort of fetuses with enlarged NT we may conclude that NIPT, depending on the approach, will miss chromosome aberrations in a significant percentage of pregnancies. Moreover all abnormal NIPT results require confirmatory studies with invasive testing, which will delay definitive diagnosis in ca. 30 % of patients. These figures are important for pretest counseling enabling pregnant women to make informed choices on the prenatal test. Larger cohorts of fetuses with an enlarged NT should be investigated to assess the additional diagnostic value of high resolution array testing for this indication. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of I. NT-BNP and clinical effect of the treatment of chronic heart failure with Qishenyiqi pills. Methods: 60 cases of patients with chronic heart failure treatment were selected and randomly divided into experimental group and control group with 30 cases in each group, the control group were treated with benazepril hydrochloride tablets 10 mg/time, 1 times/d; Furosemide Tablets 20 mg/time. 1 times /d; metoprolol sustained-release tablets 23.75 mg/time. 1 times / D; atorvastatin 20 mg/ time, 1 times /d; digoxin 0.125 mg/time, 1 times/d; Aspirin Enteric-coated Tablets 100 mg/time, Isosorbide Mononitrate Tablets 20mg/time ltime /d; the patients in the experimental group on the basis of the control group. Qishenyiqi pills, a 1 bag. 3 times /d, for 4 weeks after the end of treatment. The serum NT-BNP. patients with hs-CRP. cTn I levels were detected and compared. Results: Compared with before treatment, after treatment in patients with serum NT-BNP. hs CRP. cTnl water decreased (P<0.05); compared with the control group, patients in the experimental group the serum NT-BNP. hs CRP. cTnl level is low. clinical treatment, the total effective rate was higher (P < 0.05). Conclusion: Qi Shen Qi pill can reduce the serum levels of BNP - hs-CRP. cTn. I NT in patients with chronic heart failure, the clinical efficacy is good, it has guiding significance for clinical. [ABSTRACT FROM AUTHOR]

Reward is known to affect visual search performance. Rewarding targets can increase search performance, whereas rewarding distractors can decrease search performance. We used subcomponents of the N2pc in the event-related EEG, the NT (target negativity) and ND/PD (distractor negativity/positivity), in a visual search task to disentangle target and distractor processing related to reward. The visual search task comprised homogeneous and heterogeneous contexts in which a target and a colored distractor were embedded. After each correct trial, participants were given a monetary reward that depended on the color of the distractor. We found longer response times for displays with high-reward distractors compared to displays with low-reward distractors, indicating reward-induced interference, however, only for heterogeneous contexts. The NT component, indicative of attention deployment to the target, showed that target selection was impaired by high-reward distractors, regardless of the context homogeneity. Processing of distractors was not affected by reward in homogeneous contexts. In heterogeneous contexts, however, high-reward distractors were more likely to capture attention (ND) and required more effort to be suppressed (PD) than low-reward distractors. In sum the results showed that, despite the fact that target selection is impaired by high-reward distractors in both homogeneous and heterogeneous background contexts, high-reward distractors capture attention only in scenarios that foster attentional capture. [ABSTRACT FROM AUTHOR]

Latent inhibition (LI) is a measure of cognitive gating and refers to reduced conditioned learning when there is pre-exposure to the conditioned stimulus (CS) before it is paired with the unconditioned stimulus (US). Dysregulation of LI is associated with some neuropsychiatric disorders, including schizophrenia, and the ability to facilitate LI in rodents is a reasonably good predictive test for antipsychotic drugs. Converging evidence supports neurotensin-1 receptor (NTS1) agonists as novel drugs for schizophrenia. Therefore, we investigated the ability of a brain-penetrating, selective NTS1 agonist, PD149163, to facilitate LI in heterozygous Brattleboro rats, a strain that exhibits naturally low LI. Conditioned taste aversion to flavored water (FW; 0.1% saccharin) was induced by pairing it with malaise-inducing injections of lithium chloride (LiCl). Prior to LiCl-FW pairing, rats received subcutaneous injections of saline, or PD149163 (100 µg/kg or 200 µg/kg). Half the rats in each drug group had been allowed to drink FW the day before the LiCl-FW pairing (pre-exposed rats). Two days after pairing, the amount of FW each rat consumed was recorded. LI, defined as significantly greater FW drinking in the pre-exposed group compared with the non pre-exposed group, was exhibited only among rats that received 200 µg/kg of PD149163. These results further support NTS1 agonists as potentially novel drugs for the treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

The WTO – TRIPs Agreement regulates the principle of non- discrimination which must be complied by its member countries. There are two principle of non discrimination namely the principle of National Treatment ( NT ) and Most Favoured Nations principle (MFN). This study focus to the adoption of MFN and NT principles into Intellectual Property Rights laws of Indonesia whether it harmony with the legal system in Indonesia. This study uses the normative legal research methods by using conceptual approach and statute approach . The legal materials that studies in this research consists of the Primary Legal Materials : Act No. 19 of 2002 , Act No. No. . 15 of 2001, Act No. 14 of 2001, as well as the TRIPs Agreement. Secondary legal materials studied in this research are legal text books and law journals related to NT and MFN principle in the field of Intellectual Property Rights. . The results showed that the Principle of Non Discrimination System in the form of the principle of National Treatment (NT) expressly governed through Article 3 TRIPs Agreement and the principle of Most Favoured Nations (MFN) regulated through Article 4 TRIPS Agreement. As a member of WTO-TRIPs Agreement, Indonesia should comply and adopt the MFN and NT principles into IPR laws. Currently those principles exist implicitly and explicitly such as in the Act No. 19 of 2002, the Act No. 14 of 2001, and the Act No. 15 of 2001. Although the MFN and NT principles has already adopted, it is still need more effort to implement the principle of non Discrimination, especially in the relationship between Indonesia and other unequal size countries, between developing and developed countries.

In recent years, biosynthesis of nanoparticles using plant extract has attracted great attention owing to its cost effective, non-toxic, eco-friendly and as an alternative approach to physical and chemical methods. Nickel tungstate (NiWO 4 ) nanoparticles were synthesised via the aqueous leaf extract of Azadir achta indica plant. The prepared nanoparticles were characterized using UV–visible diffuse reflectance spectroscopy (UV–vis-DRS), fourier transform infra-red spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM) techniques. SEM results showed that plant extract modified NiWO 4 (PNT) was composed of tiny sphere in shape. XRD results revealed that the average crystallite size of PNT was smaller (12.12 nm) when compared to the bare NiWO 4 (NT) prepared using precipitation method (31.11 nm). The photocatalytic activity of NiWO 4 nanoparticles were investigated using methylene blue (MB) as a model organic pollutant under visible light irradiation. PNT showed high efficiency for the degradation of MB compared to NT. The effect of operation parameters such as initial dye concentration, pH and catalyst concentration has been investigated in detail. PNT was subjected to antimicrobial studies and significant results were obtained. [ABSTRACT FROM AUTHOR]

Introduction Neurotensin receptor 1 (NTR1) is overexpressed in many cancer types. Neurotensin (NT), a 13 amino acid peptide, is the native ligand for NTR1 and exhibits high (nM) affinity to the receptor. Many laboratories have been investigating the development of diagnostic and therapeutic radiopharmaceuticals for NTR1-positive cancers based on the NT peptide. To improve the biological performance for targeting NTR1, we proposed NT analogs with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelation system and different lengths of spacers. Methods We synthesized four NTR1-targeted conjugates with spacer lengths from 0 to 9 atoms (null (N0), β-Ala-OH (N1), 5-Ava-OH (N2), and 8-Aoc-OH (N3)) between the DOTA and the pharmacophore. In vitro competitive binding, internalization and efflux studies were performed on all four NT analogs. Based on these findings, metabolism studies were carried out on our best performing conjugate, 177 Lu-N1. Lastly, in vivo biodistribution and SPECT/CT imaging studies were performed using 177 Lu-N1 in an HT-29 xenograft mouse model. Results As shown in the competitive binding assays, the NT analogs with different spacers (N1, N2 and N3) exhibited lower IC 50 values than the NT analog without a spacer (N0). Furthermore, N1 revealed higher retention in HT-29 cells with more rapid internalization and slower efflux than the other NT analogs. In vivo biodistribution and SPECT/CT imaging studies of 177 Lu-N1 demonstrated excellent accumulation (3.1 ± 0.4%ID/g) in the NTR1-positive tumors at 4 h post-administration. Conclusions The DOTA chelation system demonstrated some modest steric inhibition of the pharmacophore. However, the insertion of a 4-atom hydrocarbon spacer group restored optimal binding affinity of the analog. The in vivo assays indicated that 177 Lu-N1 could be used for imaging and radiotherapy of NTR1-positive tumors. [ABSTRACT FROM AUTHOR]

Besides visual salience and observers' current intention, prior learning experience may influence deployment of visual attention. Associative learning models postulate that observers pay more attention to stimuli previously experienced as reliable predictors of specific outcomes. To investigate the impact of learning experience on deployment of attention, we combined an associative learning task with a visual search task and measured event-related potentials of the EEG as neural markers of attention deployment. In the learning task, participants categorized stimuli varying in color/shape with only one dimension being predictive of category membership. In the search task, participants searched a shape target while disregarding irrelevant color distractors. Behavioral results showed that color distractors impaired performance to a greater degree when color rather than shape was predictive in the learning task. Neurophysiological results show that the amplified distraction was due to differential attention deployment (N2pc). Experiment 2 showed that when color was predictive for learning, color distractors captured more attention in the search task (ND component) and more suppression of color distractor was required (PD component). The present results thus demonstrate that priority in visual attention is biased toward predictive stimuli, which allows learning experience to shape selection. We also show that learning experience can overrule strong top-down control (blocked tasks, Experiment 3) and that learning experience has a longer-term effect on attention deployment (tasks on two successive days, Experiment 4). [ABSTRACT FROM AUTHOR]

Peptide receptor radionuclide therapy (PRRT) is a site-directed targeted therapeutic strategy that specifically uses radiolabeled peptides as biological targeting vectors designed to deliver cytotoxic levels of radiation dose to cancer cells, which overexpress specific receptors. Interest in PRRT has steadily grown because of the advantages of targeting cellular receptors in vivo with high sensitivity as well as specificity and treatment at the molecular level. Recent advances in molecular biology have not only stimulated advances in PRRT in a sustainable manner but have also pushed the field significantly forward to several unexplored possibilities. Recent decades have witnessed unprecedented endeavors for developing radiolabeled receptor-binding somatostatin analogs for the treatment of neuroendocrine tumors, which have played an important role in the evolution of PRRT and paved the way for the development of other receptor-targeting peptides. Several peptides targeting a variety of receptors have been identified, demonstrating their potential to catalyze breakthroughs in PRRT. In this review, the authors discuss several of these peptides and their analogs with regard to their applications and potential in radionuclide therapy. The advancement in the availability of combinatorial peptide libraries for peptide designing and screening provides the capability of regulating immunogenicity and chemical manipulability. Moreover, the availability of a wide range of bifunctional chelating agents opens up the scope of convenient radiolabeling. For these reasons, it would be possible to envision a future where the scope of PRRT can be tailored for patient-specific application. While PRRT lies at the interface between many disciplines, this technology is inextricably linked to the availability of the therapeutic radionuclides of required quality and activity levels and hence their production is also reviewed. [ABSTRACT FROM AUTHOR]

Ribosomal RNAs in both prokaryotes and eukaryotes feature numerous repeats of three or more nucleotides with the same nucleobase (homoiterons). In prokaryotes these repeats are much more frequent in thermophile compared to mesophile or psychrophile species, and have similar frequency in both large RNAs. These features point to use of prokaryotic homoiterons in stabilization of both ribosomal subunits. The two large RNAs of eukaryotic cytoplasmic ribosomes have expanded to a different degree across the evolutionary ladder. The big RNA of the larger subunit (60S LSU) evolved expansion segments of up to 2400 nucleotides, and the smaller subunit (40S SSU) RNA acquired expansion segments of not more than 700 nucleotides. In the examined eukaryotes abundance of rRNA homoiterons generally follows size and nucleotide bias of the expansion segments, and increases with GC content and especially with phylogenetic rank. Both the nucleotide bias and frequency of homoiterons are much larger in metazoan and angiosperm LSU compared to the respective SSU RNAs. This is especially pronounced in the tetrapod vertebrates and seems to culminate in the hominid mammals. The stability of secondary structure in polyribonucleotides would significantly connect to GC content, and should also relate to G and C homoiteron content. RNA modeling points to considerable presence of homoiteron-rich double-stranded segments especially in vertebrate LSU RNAs, and homoiterons with four or more nucleotides in the vertebrate and angiosperm LSU RNAs are largely confined to the expansion segments. These features could mainly relate to protein export function and attachment of LSU to endoplasmic reticulum and other subcellular networks. [ABSTRACT FROM AUTHOR]

The paper presents an unnoticed "rule" governing the presence or absence of the article with ővoμα in naming-constructions of the type "the name of x is JV." It arises from the survival of an archaic pattern with the dative and no article, alongside a newer pattern with the genitive and the article. The "rule" is shown to operate not only in the LXX and NT but in ancient Greek generally, from Homer to Koine Greek. Observance of the "rule" indicates the LXX translators' and the NT authors' familiarity with idiomatic Greek. The "rule" can also contribute to resolving textual questions, notably Luke 1:63. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives To determine the effect of different ultrasound machine-probe combinations on nuchal translucency ( NT) measurements and to assess how this impacts on the accuracy of the NT-derived component of first-trimester screening for trisomy 21. Methods Sixteen different ultrasound machine-probe combinations were used for axial measurement of 2.0-, 3.0- and 4.0-mm spaced targets in an ultrasound phantom. Differences between the measured and known values were determined. The mean of the axial measurements was used to calculate adjusted risks for trisomy 21, given specific clinical scenarios. Results Differences observed using different machine-probe combinations for the 2.0-mm target ranged from 1.8-2.2 mm; for the 3.0-mm target, 2.7-3.2 mm; and for the 4-mm target, 3.7-4.3 mm, and exceeded those due to intraobserver variability. For a fetal crown-rump length of 50.0 mm and NT measurement of 2.0 mm, the maximum/minimum measurements in the fetus of a 40-year-old woman led to derived risks ranging from 1 in 32 ( NT, 2.2 mm) to 1 in 189 ( NT, 1.8 mm) and in the fetus of a 20-year-old with an NT of 3.0 mm these ranged from 1 in 102 ( NT, 3.2 mm) to 1 in 160 ( NT, 2.7 mm). Conclusions We have described the effect of machine-probe combinations on small but very precise ultrasound measurements. Such machine-probe combinations led to greater variability than those ascribed to intraobserver differences, and significantly affected the screening risk for the same fixed measurement. This finding has implications for Down syndrome screening algorithms and audit of ultrasound operators. Furthermore, most ultrasound machines are neither calibrated nor specified for measurements of tenths of a mm. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Labile pools of soil organic carbon (SOC) and nitrogen (N) are affecting the carbon (C) and N fluxes in the terrestrial soils, whereas long-term C and N storage is determined by the long-lived recalcitrant fractions. Tillage and subsurface drainage influences these pools; however, the effect of these systems on poorly drained soils may be different. Therefore, the present study was conducted on a field experiment, established at the Waterman Farm of the Ohio State University in 1994. Specific objectives of the study are to assess the influence of no-tillage (NT), chisel tillage (CT) with drainage (TD) and non-drainage (ND) management under a continuous corn (Zea maysL.) system on SOC, C fractions (heavy and light), and water stable aggregates (WSA). Data from this study showed that the SOC stock for the NT was 25, 37 and 32% higher for the 0–10, 10–20 and 40–60 cm depths, respectively, as compared to that under CT system. Tillage significantly influenced the light fraction (LF) and heavy fraction (HF) of carbon. The NT system increased LF and HF by 10 and 12%, respectively, compared to CT for the 0–10 cm depth. Eighteen years of NT management decreased soil bulk density and improved macroaggregates and mean weight diameter compared to that under CT system. Drainage impacts on soil parameters were negligible, and may be partially due to the reason that the corn-corn cropping system may not have sufficiently improved the soil properties between the two tillage systems. In general, drainage improved porosity and the corn yield. It can be concluded that NT with subsurface management improves SOC dynamics and promotes aggregation and corn yield as compared to that with CT system. [ABSTRACT FROM PUBLISHER]

Highlights: [•] NTc reduced wheat biomass and yield much more than NTm. [•] No-tillage increased soil bulk density, water content, organic C, but decreased EC. [•] NTc or NTm inhibited the dominant weed in wheat field. [•] Manure inputs were a viable alternative to crop residue in this no-tillage system. [ABSTRACT FROM AUTHOR]

Neurotensin (NT) is a naturally occurring neurotransmitter that mediates the metabotropic seven-transmembrane G protein-coupled receptors, namely NTR1s, richly expressed on tumor surface. Therefore, mutated active molecular fragments of NT that possess selective antagonist or weak agonist properties and the high affinity to NTR1 have attracted considerable interest for use in thrombus, inflammation, and imaging/treatment of tumors. In this work, SERS spectra of three N-terminal fragments of human NT (NT1-6, NT1-8, and NT1-11) and six specifically mutated C-terminal fragments of human NT, including NT8-13, [Dab9]NT8-13, [Lys8,Lys9]NT8-13, [Lys8-(®)-Lys9]NT8-13, [Lys9,Trp11,Glu12]NT8-13, and NT9-13, adsorbed onto nanometer-sized colloidal silver particles in an aqueous solution at pH level of the solution 2 are presented. A comparison was made between the structures of the native and mutated fragments to determine how changes in peptide length and mutations of the structure influenced the NT adsorption properties. Based on the interpretation of the obtained data, we showed that all of the investigated NT fragments, excluding [Lys9,Trp11,Glu12]NT8-13, tended to adsorb on the silver surface mainly through the L-tyrosine residue and the carboxylate group. The Tyr ring lied more-or-less flat on the silver surface. The hydrogen atom from the phenol group dissociated upon binding. On the other hand, [Lys9,Trp11,Glu12]NT8-13 bound to this substrate through the close to vertical co-pyrrole ring of the indole ring (Trp11) and -COO-. Comparison of the presented data with those obtained earlier for NT allows to suggest that in the case of naturally occurring neurotensin, both Tyr residues together with the carboxylate group play crucial role in the binding to the nanometer-sized colloidal silver particles. This geometry of binding forces the NT molecule to lay flat on the surface. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article discusses a study on the external validity of the extant heart failure (HF) risk scores namely the Framingham Heart Study and Health ABC scores in the a large biracial cohort of middle-aged participants taken from 4 U.S. communities by the Athero-sclerosis Risk in Communities (ARIC) Study. Fifteen thousand seven hundred ninety two women and men aged 45 to 64 years were enrolled. It concludes that ARIC HF risk score can predict 10 year risk of hospitalized HF in community settings.

Abstract: Background: To investigate flow in the ductus venosus at 11–13 + 6 weeks of gestation in women with normal pregnancies in the Taiwanese population. Methods: Two hundred and fifty-two normal singleton pregnancies with gestational ages ranging from 11 to 13 + 6 weeks were examined in this study. The pulsatility index for veins (PIV), resistance index (RI), peak velocity during ventricular systole (S-wave), and peak velocity during ventricular diastole (D-wave) were recorded from the ductus venosus. Results: We analyzed 252 participants who all fulfilled the inclusion and exclusion criteria of our study. The mean maternal age was 31 (range 19–45 years), with a corresponding gestational age of 12 + 4 weeks (range 11–13 + 6). No significant change was found in the vascular indices as gestational age increased for the S-wave (S-wave = 1.4214 (GA) + 17.448, r = 0.09, P = 0.154), PIV (PIV = −0.0358 (GA) + 1.4143, r = −0.05, P = 0.378) and RI (RI = −0.035 (GA) + 1.1478, r = −0.064, P = 0.468). In contrast, the D-wave behaved differently from the other variables. There was a significant increase (r = 0.155, P = 0.013) in the D-wave with gestational age (D-wave = 1.4896 (GA) – 7.1547). Conclusion: D-wave velocity in the ductus venosus increased with gestational age. S-wave peak velocity showed an increasing trend and PIV showed a decreasing trend with gestational age, but they did not reach statistical significance. [Copyright &y& Elsevier]

Abstract: Human thymus of healthy subjects and patients affected by thymoma-associated Myastenia Gravis were studied in order to visualize and compare the morphological distributive pattern of four neuropeptides: vasoactive intestinal peptide, substance P, neuropeptide Y, and neurotensin. Based on our observations, we formulated hypotheses on their relations in neuro-immunomodulation under physiological and pathophysiological conditions. Immuno-histochemical staining for neuropeptides was performed and morphological and morphometrical analyses were conducted on healthy and diseased thymus. In normal thymus, a specific distributive pattern was observed for the several neuropeptide-positive nerves in different thymus lobular zones. In particular substance P-positive fibers were observed in subcapsular zone, specifically located into parenchyma, where they represent the almost total amount of fibers; neurotensin-positive fibers were observed primarily located in parenchyma than perivascular site of several thymus lobular zones, and more abundant the cortico-medullary and medullary zones. Instead VIP- and NPY-positive fibers were widely distributed in perivascular and parenchymal sites of several thymus lobular zones. In thymoma, the distribution of neuropeptide-positive fibers was quantitatively reduced, while cells immunopositive to VIP and substance P were quantitatively increased and dispersed. Observation of the perivascular and parenchymal distribution of the analyzed neuropeptides suggests evidence that a regulatory function is performed by nerves and cells that secrete neuropeptide into the thymus. The alteration of neuropeptide patterns in thymoma suggests that these neurotransmitters play a role in autoimmune diseases such as Myastenia Gravis. [Copyright &y& Elsevier]

Ferroelectric films with three different typical structures, Pb(Zr0.52Ti0.48)O3 (PZT) with Perovskite, SrBi2Ta2O9 (SBT) with layered-Perovskite, and Nd2Ti2O7 (NT) with pseudo-pyrochlore, were prepared on Y2O3 to form a metal-ferroelectric-insulator-semiconductor structure. Our work involves understanding the relationships between retention properties and ferroelectric properties including interface and layer uniformity and insulator layer. NT possessed a relatively larger memory window and better retention property than SBT and PZT. Low permittivity, high coercive field, stable interface, and phase formation without compositional deviation from stoichiometry were found to be the most important control factors for a ferroelectric field effect transistor. [ABSTRACT FROM AUTHOR]

Abstract: Several studies carried out in the last years have demonstrated the presence of a wide range of contaminants in some areas of the Venice Lagoon. Many of these contaminants are able to drive free radical reactions, which lead to oxidative stress and can potentially affect fish health. In the present study, oxidative stress biomarkers were examined in three different sites (Porto Marghera, Val di Brenta and Caroman) of the Venice Lagoon and their levels monitored in Zosterisessor ophiocephalus, one of the most common fish species present in the lagoon. Schmorl''s staining revealed the presence of melanomacrophage centres in spleen and head kidney, and the highest number of melanomacrophage centres was observed in the animals sampled at the Porto Marghera (Porto Marghera vs Val di brenta and Caroman: p <0.01). The cellular localization of HNE and NT, investigated through an immunohistochemical approach, showed that immunopositivity was mainly localized in melanomacrophage centres of spleen and kidney. It is relevant that the animals of the detoxified control group did not exhibit any immunoreactivity. By Western blot, the antibodies against HNE and NT recognized in the liver polypeptides damaged by oxidative stress with molecular weights under 66kDa. Comparing the relative densities, animals from the Val di Brenta site exhibited the lowest levels of HNE adducts (p <0.05), whereas animals from the Porto Marghera site exhibited the highest levels of NT adducts (p <0.05). MDA levels, measured spectrophotometrically by TBARS assay did not exhibit any statistical difference among sites. [Copyright &y& Elsevier]

Abstract: Leptin signaling in the hypothalamus is required for normal food intake and body weight homeostasis. Recent evidence suggests that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways mediate leptin signaling in the hypothalamus. We have previously demonstrated that leptin stimulates phosphodiesterase-3B (PDE3B) activity in the hypothalamus, and PDE3 inhibitor cilostamide reverses anorectic and body weight reducing effects of leptin. To establish the physiological role of PDE3B signaling in the hypothalamus, we examined if leptin signaling through the PDE3B pathway is responsible for the activation of proopiomelanocortin (POMC) and neurotensin (NT) neurons, which are known to play a critical role in energy homeostasis. To this end, we assessed the effect of cilostamide on leptin-induced POMC and NT gene expression in the rat hypothalamus. Results showed that while central injection of leptin significantly increased both POMC and NT mRNA levels in the medial basal hypothalamus, cilostamide completely reversed this effect of leptin suggesting a PDE3B-activation dependent induction of POMC and NT gene expression by leptin. This result further suggests that the PDE3B pathway plays an important role in mediating leptin action in the hypothalamus. [Copyright &y& Elsevier]

The fact that, cloning using somatic cell nuclear transfer (SCNT) method has been performed, opened new horizons for cloning, and changed the way of our understanding and approach to cell and nucleus. The progress in cloning technology, brought the anticipation of the ability to clone an organism from each somatic cell nucleus. Therefore, the ‘Cell Theory’ is about to take the additional statement as "An organism arises from every nucleus". The development of gene targeting procedures which can be applied with SCNT, showed us that it may be possible to obtain different versions of the original genetic constitution of a cell. Because of this opportunity which is provided by SCNT, in reproductive cloning, it would be possible to clone enhanced organisms which can adapt to different environmental conditions and survive. Furthermore, regaining the genetic characteristics of ancestors or reverse herediter variations would be possible. On the other hand, in therapeutic cloning, more precise and easily obtainable alternatives for cell replacement therapy could be presented. However, while producing healthier or different organisms from a nucleus, it is hard to foresee the side effects influencing natural processes in long term is rather difficult. [ABSTRACT FROM AUTHOR]

Copyright of Progresos en Diagnóstico y Tratamiento Prenatal is the property of Grupo ARS XXI de Comunicacion, S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. While hyperleptinemia in obese people suggests a state of leptin resistance, the mechanism is not clearly understood. In a rat model of central leptin infusion in which animals develop resistance to the satiety action of leptin, orexigenic peptide producing neuropeptide Y neurons in the hypothalamus develop leptin resistance. However, it is still unknown if increased hypothalamic leptin tone caused by central leptin infusion results in the development of leptin resistance in anorexigenic peptide producing proopiomelanocortin (POMC) and neurotensin (NT) neurons. To this end, male rats were infused chronically with leptin (160ng/h) or vehicle into the lateral cerebroventricle for 16 days. On day 4 of leptin infusion when food intake was decreased, POMC and NT mRNA levels, as determined by RNAse protection assay, were significantly increased as compared to control. By contrast, on day 16 of leptin infusion, when food intake was mostly normalized, both POMC and NT mRNA levels remained unchanged compared with control. These findings suggest the development of leptin resistance in the POMC and NT neurons following chronic elevation of hypothalamic leptin tone, which may be involved in the development of resistance to the satiety action of leptin following central infusion of this peptide hormone. [Copyright &y& Elsevier]

The article investigates the clinical utility of the first-trimester markers of aneuploidy in their ability to predict preterm delivery. Results reveal that low levels of maternal serum pregnancy-associated plasma protein-A (PAPP-A) are related to an increased risk of preterm or early preterm delivery. The likelihood ratios (LR) profiles offered at various levels of PAPP-A may be helpful in counseling women with such results.

The article presents a study that examines the clinical utility of the first-trimester biochemical markers of aneuploidy in their ability to predict subsequent delivery of a small-for-gestational age infant. The methods and results of the study are discussed. In conclusion, low levels of maternal serum PAPP-A are associated with increased risk for subsequent delivery of an small-for-gestational infant.

Abstract: Gene transfer events from organelle genomes (mitochondria and chloroplasts in plants) to the nuclear genome are important processes in the evolution of the eukaryotic cell. It is highly likely that the gene transfer event is still an ongoing process in higher plant mitochondria and chloroplasts. The number and order of genes encoded in the chloroplast genome of higher plants are highly conserved. Recently, several exceptional cases of gene loss from the chloroplast genome have been discovered as the number of complete chloroplast genome sequences has increased. The Populus chloroplast genome has lost the rpl32 gene, while the corresponding the chloroplast rpl32 (cp rpl32) gene has been identified in the nuclear genome. Nuclear genes transferred from the chloroplast genome need to gain a sequence that encodes a transit peptide. Here, we revealed that the nuclear cp rpl32 gene has acquired the exon sequence, which is highly homologous to a transit peptide derived from the chloroplast Cu–Zn superoxide dismutase (cp sod-1) gene. The cp rpl32 gene has acquired the sequence that encodes not only for the transit peptide, but also for the conserved N-terminal portion of the mature SOD protein from the cp sod-1 gene, suggesting the occurrence of DNA sequence duplication. Unlike cp SOD-1, cp RPL32 did not show biased localization in the chloroplasts. This difference may be caused by mutations accumulated in the sequence of the SOD domain on the cp rpl32 gene. We provide new insight into the fate of the inherent sequence derived from a transit peptide. [Copyright &y& Elsevier]

Objectives: To study the outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency thickness (NT), with respect to fetal loss, structural defects and genetic syndromes with developmental delay, and to provide information that would be helpful for parental counseling on the residual risk of adverse outcome when ultrasound findings are normal. Methods: We reviewed the outcome of all pregnancies presenting at the Academic Medical Centre in Amsterdam with increased NT between January 1994 and March 2005. Fetal karyotyping and two-step ultrasound investigation at 13-18 and 20-24 weeks' gestation were offered in all cases. Particular attention was paid to the relationship between normal karyotype, ultrasound findings at the 20-24-week scan and subsequent pregnancy outcome. An adverse outcome was defined as miscarriage, intrauterine death, termination of pregnancy at parental request or the finding of one or more structural defects or genetic disorders. Results: A total of 675 fetuses with increased NT, known karyotype and known pregnancy outcome was analyzed. A chromosomal anomaly was detected in 224 (33%) fetuses. In 451 (67%) fetuses, the karyotype was normal. The overall incidence of an adverse pregnancy outcome in this group was 19% and, when analyzed according to the initial degree of increase in NT, the likelihood of an adverse outcome increased with increasing NT, ranging from 8% to 80%. 425 fetuses underwent a detailed second-trimester ultrasound scan. Anomalies were detected, at the time of ultrasound or after birth, in 54 (13%) of these fetuses (17 isolated cardiac defects, 14 other structural defects and 23 genetic disorders). An adverse pregnancy outcome was recorded in 4% of cases in which there were normal findings at the 20-week scan. Seven of these cases were classified as 'potentially amenable' to ultrasound detection. With exclusion of these cases, the chance of a healthy baby, if the 20-week scan was completely normal, was 98%. Genetic syndromes with dysmorphic features and neurodevelopmental delay occurred in seven (1.6%) of the fetuses with normal karyotype. In three of these pregnancies, non-specific suspicious ultrasound findings (nuchal edema, mild pyelectasis, pericardial effusion) were observed at the mid-trimester scan and in two others, subtle cardiac defects were detected after delivery. In the remaining two cases (0.5%) the mid-trimester scan was completely normal and no structural defects were observed after delivery. Conclusion: After exclusion of chromosomal anomalies, one out of five fetuses with increased NT has an adverse pregnancy outcome. The chance of an uneventful pregnancy outcome depends on the initial degree of increase in NT. However, if the detailed ultrasound examination at around 20 weeks is normal, a favorable outcome can be expected with confidence, irrespective of initially increased NT. [ABSTRACT FROM AUTHOR]

Objectives To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict future fetal loss. Methods We examined 54 722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness, maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the expected normal median for a pregnancy of the same gestation (MoM) and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length (CRL). The association between free β-hCG, PA PP-A and delta NT and the incidence of fetal loss prior to 24 weeks, at or after 24 weeks or at any time, was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratio (LR) for fetal loss was also calculated. Results The rate of fetal loss increased with decreasing maternal serum free β-hCG and PA PP-A and increasing delta NT. At the 5th centile of the normal outcome group for free β-hCG (0.41 MoM) the odds ratio for fetal loss before 24 weeks, at or above 24 weeks and at any gestation was 3.1, 1.8 and 2.6, respectively. The respective values for the 5th centile of PAPP-A (0.415 MoM) were 3.3, 1.9 and 2.8 and for the 95th centile of delta NT they were 2.5, 1.9 and 2.2, respectively. There was almost no correlation between reduced levels (≤0.50 MoM) of PAPP-A and reduced levels of free β-hCG in either the normal pregnancy group (r = 0.041) or the group with fetal death (r = 0.0 72), indicating relatively independent prediction by either biochemical marker. Conclusions Low levels of maternal serum PAPP-A and free β-hCG and increased fetal NT are associated, in the absence of an abnormal karyotype, with an increased risk of impending fetal death. The likelihood ratio profiles provided at various levels of PAPP-A or free β-hCG may be of some help in counseling women with such results and raise awareness among health-care professionals for increased surveillance in such cases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of verteporfin therapy (Visudyne) on age-related macular degeneration (AMD) in Chinese patients. The baseline characteristic and the visual outcome will be compared with the treatment of AMD with photodynamic therapy study (TAP) and verteporfin in photodynamic therapy study (VIP).Design: Retrospective comparative case series.Method: We recruited patients >50 years old, with best-corrected visual acuity >20/200 and fluorescein angiography documenting subfoveal either predominantly classic with greatest linear dimension <5400 mum or pure occult choroidal neovascularization (CNV) secondary to AMD. We applied non-thermal laser to the lesion 15 min after visudyne infusion as described in TAP study. Patients were followed up with fluorescein angiography every 3 months. Additional treatment would be offered if there was evidence of recurrence of CNV.Outcome Measure: Baseline characteristic and visual outcome.Result: In all, 46 eyes of 42 patients were enrolled at our centre from July 2002 to June 2003. They comprised 11 eyes with predominantly classic lesions and 35 eyes with pure occult lesion. The mean number of treatment sessions given was 2.9 in the first year. At the 12-month examination, there were 63 and 29% of patients showing visual improvement in predominantly classic and occult groups, respectively, while there were only 16% of patients in the TAP study and 12% of patients in the VIP study showing visual improvement in the same period.Conclusion: Verteporfin therapy for subfoveal CNV is beneficial to Chinese patients with AMD at first year. The visual result seems to be better than that observed in Caucasian patients. [ABSTRACT FROM AUTHOR]

Nuchal translucency (NT) describes an echo-free area, below the skin, in the posterior nuchal and back region of the fetus and is typically observed in the first and early second trimester of pregnancy. A wide NT has been correlated with chromosomal and congenital abnormalities in the fetus. An accurate NT measurement is a critical component of the estimation of Down syndrome risk in the first trimester of pregnancy and the Nuchal Translucency Quality Review Program (NTQR) identified nine criteria that ensure an accurate measurement of NT during ultrasound examination. The purpose of this chapter is to present the technical aspects of obtaining an accurate NT measurement on ultrasound as outlined by the NTQR. [Copyright &y& Elsevier]

Abstract: Recent progress in reproductive biology has improved comprehension physiology of the spermatozoa and on the fertilization mechanisms. This new knowledge has carried out the elaboration of tests on male fertility based on sperm genomic integrity. This review presents some of these techniques and brings a reflexion element on the application and use of sperm DNA integrity in the investigation of male fertility. The single cell gel electrophoresis (COMET assay), Sperm Chromatin Structure Assay (SCSA), In Situ Nick Translation (NT: Nick Translation) and Terminal Uridine Nick-End Labelling (TUNEL assay) are actually the most currently used techniques for the measure of sperm DNA integrity in research clinic. From a certain point of view, TUNEL assay, SCSA, COMET assay and NT assay are complementary. The TUNEL and COMET can measure single and double strand breaks of DNA, the SCSA can detect the abnormalities in the chromatin compaction and the NT assay can detect the single strand breaks of DNA. The exact origin of sperm DNA fragmentation is not established yet. However, several mechanisms have been proposed: defect in the chromatin compaction during spermiogenesis; reactive oxygen species production by immature spermatozoa; apoptosis during spermatogenesis. It becomes important to consider the possible consequences of the oocyte fertilization by a spermatozoon having a high degree of DNA fragmentation. The use in routine of some of these tests must however pass by a standardization of the inter laboratory protocols and obviously, by the establishment of both in vivo and in vitro discriminating threshold values in order for these tests to present a good predictive value for pregnancy outcome. [Copyright &y& Elsevier]

To study the DNA methylation events in normal and cloned rabbit embryos, we investigated the methylation status of a satellite sequence and the promoter region of a single-copy gene using bisulfite-sequencing technology. During normal rabbit embryo development, both sequences maintained hypermethylation status until the 8- to 16-cell stage when progressive demethylation took place. In cloned embryos, the single-copy gene promoter sequence was rapidly demethylated and precociously de novo methylated, while the satellite sequence maintained the donor-type methylation status in all examined stages. Our results indicate that unique sequences as well as satellite sequences may have aberrant methylation patterns in cloned embryos. [Copyright &y& Elsevier]

Streptococcus pneumoniae has re-emerged as a major cause of morbidity and mortality throughout the world and its continuous increase in antimicrobial resistance is rapidly becoming a leading cause of concern for public health. This review is focussed on the analysis of recent insights on the study of capsular polysaccharide biosynthesis, and cell wall (murein) hydrolases, two fundamental pneumococcal virulence factors. Besides, we have also re-evaluated the molecular biology of the pneumococcal phage, their possible role in pathogenicity and in the shaping of natural populations of S. pneumoniae. Precise knowledge of the topics reviewed here should facilitate the rationale to move towards the design of alternative ways to combat pneumococcal disease. [Copyright &y& Elsevier]

Objective The aim of this study was to investigate the natural course of enlarged nuchal translucency (NT) and to determine if its disappearance before 14 weeks' gestation is a favorable prognostic sign in relation to fetal karyotype and pregnancy outcome. Methods A total of 147 women with increased NT (> 95th centile) at first measurement were included in this study. A second measurement was performed in all cases, at an interval of at least 2 days. Both measurements were taken between 10 + 3 and 14 + 0 weeks. All women underwent chorionic villus sampling or amniocentesis for subsequent karyotyping. In those women with a normal karyotype, a fetal anomaly scan was performed at 20 weeks' gestation. Pregnancy outcome was recorded in all cases. The finding of persistent or disappearing NT enlargement was analyzed in relation to fetal karyotype and pregnancy outcome. Results Of the 147 paired measurements, NT remained enlarged at the second measurement in 121 (82%) cases. An abnormal karyotype was found in 35% of these cases. In 26 (18%) fetuses the NT measurement was found to be below the 95th percentile at the second measurement and in only two of them an abnormal karyotype was found (8%). In the 103 chromosomally normal fetuses an adverse outcome (i.e. fetal loss or structural defects) was recorded in 22 fetuses with persistent enlargement (28%) and in four fetuses with disappearing enlargement (17%). Conclusions Disappearance of an enlarged NT before 14 weeks' gestation is not a rare phenomenon and seems to be a favorable prognostic sign with respect to fetal karyotype. Overall, no significant difference in pregnancy outcome was found between chromosomally normal fetuses with persisting or disappearing NT enlargement. [ABSTRACT FROM AUTHOR]

The involvement of inducible nitric oxide synthase (iNOS) and nitrotyrosine (NT) in pathogenesis of toxocaral granulomatous hepatitis (TGH) in a murine host was quantitatively determined by biochemical, parasitological, pathological, and immunohistochemical assessments in a 42-week investigation. Mice were sacrificed for serum collection and histological processing as well as acid–pepsin digestion of the liver in a larval recovery study. Significantly increased levels of total serum NO were found in the trial, indirectly suggesting iNOS activation in the liver. iNOS reactivity was predominantly observed in infiltrating leucocytes in lesions and normal and apocrine-like cholangiocytes; in contrast, hepatocytes and multinucleated giant cells showed negative cytoplasmic staining in TGH. Strong iNOS-like reactivity was also detected on the body wall of larvae. The locations of NT reactivity were nearly identical to those of iNOS expression; infiltrating leucocytes or cholangiocytes stained for iNOS were also stained for NT in TGH. Enhanced iNOS expression, but not invading larvae (r =  0·256,P  = 0·211), seemed to play a certain role in pathological damage in TGH due to a significant correlation between iNOS expression and serum alanine aminotransferase (ALT) levels (r = 0·593,P  = 0·021) in the trial. Our present results indicate a potential therapeutic strategy for treatment of GH caused by other nematodes through manipulation of iNOS expression. [ABSTRACT FROM AUTHOR]

: ObjectivesWe sought to investigate whether two polymorphisms located in the promoter (T-786C) and exon 7 (Glu298Asp) of the endothelial nitric oxide (NO) synthase (eNOS) gene affected agonists-mediated NO release.: BackgroundEndothelial dysfunction can be genetically determined. Therefore, we investigated whether two polymorphisms located in the eNOS gene affected agonists-mediated NO release.: MethodsWe compared endothelial-dependent and -independent vasodilation of the different eNOS genotypes in a cross-sectional study on 187 subjects, of whom 137 were uncomplicated essential hypertensive patients (PH) (49 ± 9 years, 151 ± 11/99 ± 5 mm Hg) and 50 healthy normotensive subjects (NT) (43 ± 16 years, 123 ± 10/78 ± 7 mm Hg). Endothelial-dependent and -independent vasodilation was assessed as the forearm blood flow response to incrementally increasing doses of acetylcholine (0.15, 0.45, 1.5, 4.5, 15 μg/100 ml/min) and sodium nitroprusside (1, 2, 4 μg/100 ml/min), respectively. Genotyping was performed with melting curve analysis (Lightcycler) of polymerase chain reaction products from acceptor (5′ end-labeled with LCRed 640) and donor probes (3′ end-labeled with fluorescein) specific for each polymorphism.: ResultsThe genotype distribution of T-786C (CC = 21.9%, CT = 48.7%, TT = 29.4%) and Glu298Asp (GG = 39.0%, GT =51.9%, TT = 9.1%) was similar in PH and NT. A repeated measure analysis of variance showed a blunting of endothelium-dependent vasodilation in PH compared with NT (p < 0.001). A significant effect of the T-786C (p = 0.002) but not of the Glu298Asp (p = NS) eNOS polymorphism on endothelial-dependent vasodilation was found. However, we also detected a significant interaction between the T-786C and Glu298Asp polymorphism (p < 0.001). No effect on either polymorphism on endothelial-independent vasodilation was seen.: ConclusionsThe T-786C promoter polymorphism and its interaction with exon 7 Glu298Asp affect endothelium-dependent vasodilation in mild-to-moderate PH patients and NT Caucasian subjects. [Copyright &y& Elsevier]