One-Pot Synthesis of Polycyclic Nucleosides with Unusual Molecular Skeletons

An R hydroxy pyrrolidine tricyclic nucleoside 3 and its spontaneous reaction with acetone is described. In this transformation highly functionalized polycyclic nucleosides with rather unusual molecular skeletons are formed in a complete regio-and stereoselective way. The reaction involves the formation of three new bonds, two of them novel carbon-carbon bonds, in a one-pot way. An enamine-iminium mechanism with participation of carbinolamine, iminium ion, and enamine intermediates is proposed as a plausible explanation for this transformation. The scope of the reaction is briefly studied concluding that the nature of the ketone (R1COR2) is critical for the initial attack of the NH to the carbonyl group.We thank Susana Ruiz for excellent technical assistance. The Spanish MEC/MCINN (project SAF 2006-12713-C02-01) and the Comunidad de Madrid (project BIPEDD-CM S-B10-0214-2006) are also acknowl- edged for financial support. The Spanish Consejo Superior de Investigaciones Cientı´ ficas is also acknowledged for a JAE-Doc contract to M.-C.B.Peer reviewe

CSTX-1, a toxin from the venom of the hunting spider Cupiennius salei, is a selective blocker of L-type calcium channels in mammalian neurons

The inhibitor cystine-knot motif identified in the structure of CSTX-1 from Cupiennius salei venom suggests that this toxin may act as a blocker of ion channels. Whole-cell patch-clamp experiments performed on cockroach neurons revealed that CSTX-1 produced a slow voltage-independent block of both mid/low- (M-LVA) and high-voltage-activated (HVA) insect Cav channels. Since C. salei venom affects both insect as well as rodent species, we investigated whether Cav channel currents of rat neurons are also inhibited by CSTX-1. CSTX-1 blocked rat neuronal L-type, but no other types of HVA Cav channels, and failed to modulate LVA Cav channel currents. Using neuroendocrine GH3 and GH4 cells, CSTX-1 produced a rapid voltage-independent block of L-type Cav channel currents. The concentration-response curve was biphasic in GH4 neurons and the subnanomolar IC50 values were at least 1000-fold lower than in GH3 cells. L-type Cav channel currents of skeletal muscle myoballs and other voltage-gated ion currents of rat neurons, such as INa(v) or IK(v) were not affected by CSTX-1. The high potency and selectivity of CSTX-1 for a subset of L-type channels in mammalian neurons may enable the toxin to be used as a molecular tool for the investigation of this family of Cav channels. © 2007 Elsevier Ltd. All rights reserved

Data-Oriented Declarative Language for Optimizing Business Processes

There is a signifi cant number of declarative languages to describe business processes. They tend to be used when business processes need to be fl exible and adaptable, being not possible to use an imperative description. Declarative languages in business process have been traditionally used to describe the order of activities, specifi cally the order allowed or prohibited. Unfortunately, none of them is worried about a declarative description of exchanged data between the activities and how they can infl uence the model. In this paper, we analyse the data description capacity of a variety of declarative languages in business processes. Using this analysis, we have detected the necessity to include data exchanged aspects in the declarative descriptions. In order to solve the gap, we propose a Data-Oriented Optimization Declarative LanguagE, called DOODLE, which includes the process requirements referred to data description, and the possibility to include an optimization function about the process output data

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Sign-reversal of the in-plane resistivity anisotropy in hole-doped iron pnictides

The in-plane anisotropy of the electrical resistivity across the coupled orthorhombic and magnetic transitions of the iron pnictides has been extensively studied in the parent and electron-doped compounds. All these studies universally show that the resistivity $\rho_{a}$ across the long orthorhombic axis $a_{O}$ - along which the spins couple antiferromagnetically below the magnetic transition temperature - is smaller than the resistivity $\rho_{b}$ of the short orthorhombic axis $b_{O}$, i. e. $\rho_{a}<\rho_{b}$. Here we report that in the hole-doped compounds Ba$_{1-x}$K$_{x}$Fe$_{2}$As$_{2}$, as the doping level increases, the resistivity anisotropy initially becomes vanishingly small, and eventually changes sign for sufficiently large doping, i. e. $\rho_{b}<\rho_{a}$. This observation is in agreement with a recent theoretical prediction that considers the anisotropic scattering of electrons by spin-fluctuations in the orthorhombic/nematic state.Comment: This paper has been replaced by the new version offering new explanation of the experimental results first reported her

Women’s pelvic floor muscle strength and urinary and anal incontinence after childbirth: a cross-sectional study

Abstract OBJECTIVE To analyse pelvic floor muscle strength (PFMS) and urinary and anal incontinence (UI and AI) in the postpartum period. METHOD Cross-sectional study carried out with women in their first seven months after child birth. Data were collected through interviews, perineometry (Peritron™), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). RESULTS 128 women participated in the study. The PFMS mean was 33.1 (SD=16.0) cmH2O and the prevalence of UI and AI was 7.8% and 5.5%, respectively. In the multiple analyses, the variables associated with PFMS were type of birth and cohabitation with a partner. Newborn’s weight, previous pregnancy, UI during pregnancy, and sexual activity showed an association with UI after child birth. Only AI prior to pregnancy was associated with AI after childbirth. CONCLUSION Vaginal birth predisposes to the reduction of PFMS, and caesarean section had a protective effect to its reduction. The occurrence of UI during pregnancy is a predictor of UI after childbirth, and women with previous pregnancies and newborns with higher weights are more likely to have UI after childbirth.AI prior to pregnancy is the only risk factor for its occurrence after childbirth. Associations between PFMS and cohabitation with a partner, and between UI and sexual activity do not make possible to conclude that these variables are directly associated

Electrophysiological evaluation of phrenic nerve injury during cardiac surgery – a prospective, controlled, clinical study

BACKGROUND: According to some reports, left hemidiaphragmatic paralysis due to phrenic nerve injury may occur following cardiac surgery. The purpose of this study was to document the effects on phrenic nerve injury of whole body hypothermia, use of ice-slush around the heart and mammary artery harvesting. METHODS: Electrophysiology of phrenic nerves was studied bilaterally in 78 subjects before and three weeks after cardiac or peripheral vascular surgery. In 49 patients, coronary artery bypass grafting (CABG) and heart valve replacement with moderate hypothermic (mean 28°C) cardiopulmonary bypass (CPB) were performed. In the other 29, CABG with beating heart was performed, or, in several cases, peripheral vascular surgery with normothermia. RESULTS: In all patients, measurements of bilateral phrenic nerve function were within normal limits before surgery. Three weeks after surgery, left phrenic nerve function was absent in five patients in the CPB and hypothermia group (3 in CABG and 2 in valve replacement). No phrenic nerve dysfunction was observed after surgery in the CABG with beating heart (no CPB) or the peripheral vascular groups. Except in the five patients with left phrenic nerve paralysis, mean phrenic nerve conduction latency time (ms) and amplitude (mV) did not differ statistically before and after surgery in either group (p > 0.05). CONCLUSIONS: Our results indicate that CPB with hypothermia and local ice-slush application around the heart play a role in phrenic nerve injury following cardiac surgery. Furthermore, phrenic nerve injury during cardiac surgery occurred in 10.2 % of our patients (CABG with CPB plus valve surgery)

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection