Inter- and intramolecular enantioselective carbolithiation reactions

In this review we summarize recent developments in inter- and intramolecular enantioselective carbolithiation reactions carried out in the presence of a chiral ligand for lithium, such as (-)-sparteine, to promote facial selection on a C=C bond. This is an attractive approach for the construction of new carbon-carbon bonds in an asymmetric fashion, with the possibility of introducing further functionalization on the molecule by trapping the reactive organolithium intermediates with electrophiles.

Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk

Background: Vitamin K has been related to glucose metabolism, insulin sensitivity and diabetes. Because inflammation underlies all these metabolic conditions, it is plausible that the potential role of vitamin K in glucose metabolism occurs through the modulation of cytokines and related molecules. The purpose of the study was to assess the associations between dietary intake of vitamin K and peripheral adipokines and other metabolic risk markers related to insulin resistance and type 2 diabetes mellitus. Methods: Cross-sectional and longitudinal assessments of these associations in 510 elderly participants recruited in the PREDIMED centers of Reus and Barcelona (Spain). We determined 1-year changes in dietary phylloquinone intake estimated by food frequency questionnaires, serum inflammatory cytokines and other metabolic risk markers. Results: In the cross-sectional analysis at baseline no significant associations were found between dietary phylloquinone intake and the rest of metabolic risk markers evaluated, with exception of a negative association with plasminogen activator inhibitor-1. After 1-year of follow-up, subjects in the upper tertile of changes in dietary phylloquinone intake showed a greater reduction in ghrelin (-15.0%), glucose-dependent insulinotropic peptide (-12.9%), glucagon-like peptide-1 (-17.6%), IL-6 (-27.9%), leptin (-10.3%), TNF (-26.9%) and visfatin (-24.9%) plasma concentrations than those in the lowest tertile (all p<0.05). Conclusion: These results show that dietary phylloquinone intake is associated with an improvement of cytokines and other markers related to insulin resistance and diabetes, thus extending the potential protection by dietary phylloquinone on chronic inflammatory diseases.

Multi-drug resistance profiles and the genetic features of Acinetobacter baumannii isolates from Bolivia

Introduction: Acinetobacter baumannii is opportunistic in debilitated hospitalised patients. Because information from some South American countries was previously lacking, this study examined the emergence of multi-resistant A. baumannii in three hospitals in Cochabamba, Bolivia, from 2008 to 2009. Methodology: Multiplex PCR was used to identify the main resistance genes in 15 multi-resistant A. baumannii isolates. RT-PCR was used to measure gene expression. The genetic environment of these genes was also analysed by PCR amplification and sequencing. Minimum inhibitory concentrations were determined for key antibiotics and some were determined in the presence of an efflux pump inhibitor, 1-(1-napthylmethyl) piperazine. Results: Fourteen strains were found to be multi-resistant. Each strain was found to have the bla(OXA-58) gene with the ISAba3-like element upstream, responsible for over-expression of the latter and subsequent carbapenem resistance. Similarly, ISAba1, upstream of the bla(ADC) gene caused over-expression of the latter and cephalosporin resistance; mutations in the gyrA(Ser83 to Leu) and parC (Ser-80 to Phe) genes were commensurate with fluoroquinolone resistance. In addition, the adeA, adeB efflux genes were over-expressed. All 15 isolates were positive for at least two aminoglycoside resistance genes. Conclusion: This is one of the first reports analyzing the multi-drug resistance profile of A. baumannii strains isolated in Bolivia and shows that the over-expression of thebla(OXA-58), bla(ADC) and efflux genes together with aminoglycoside modifying enzymes and mutations in DNA topoisomerases are responsible for the multi-resistance of the bacteria and the subsequent difficulty in treating infections caused by them.

Framework for the Shape Optimization of Aerodynamic Profiles Using Genetic Algorithms

This study developed a framework for the shape optimization of aerodynamics profiles using computational fluid dynamics (CFD) and genetic algorithms. Agenetic algorithm code and a commercial CFD code were integrated to develop a CFD shape optimization tool. The results obtained demonstrated the effectiveness of the developed tool. The shape optimization of airfoils was studied using different strategies to demonstrate the capacity of this tool with different GA parameter combinations.

Synthetic scope and DFT analysis of the chiral binap-gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

he 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(S-a)-Binap.AuTFA](2). The alanine-derived oxazolone only reacts with tert-butyl acrylate giving anomalous regiochemistry, which is explained and supported by Natural Resonance Theory and Nucleus Independent Chemical Shifts calculations. The origin of the high enantiodiscrimination observed with maleimides and tert-butyl acrylate is analyzed using DFT computed at M06/Lanl2dz//ONIOM(b3lyp/Lanl2dz:UFF) level. Several applications of these cycloadducts in the synthesis of new proline derivatives with a 2,5-trans-arrangement and in the preparation of complex fused polycyclic molecules are described.

Evaluation of Alpha 1-Antitrypsin and the Levels of mRNA Expression of Matrix Metalloproteinase 7, Urokinase Type Plasminogen Activator Receptor and COX-2 for the Diagnosis of Colorectal Cancer

8 p.

Molecular Techniques for Dicistrovirus Detection without RNA Extraction or Purification

Dicistroviridae is a new family of small, nonenveloped, and +ssRNA viruses pathogenic to both beneficial arthropods and insect pests as well. Triatoma virus (TrV), a dicistrovirus, is a pathogen of Triatoma infestans (Hemiptera: Reduviidae), one of the main vectors of Chagas disease. In this work, we report a single-step method to identify TrV, a dicistrovirus, isolated from fecal samples of triatomines. The identification method proved to be quite sensitive, even without the extraction and purification of RNA virus.

Janus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis

Microglia are the resident brain macrophages and they have been traditionally studied as orchestrators of the brain inflammatory response during infections and disease. In addition, microglia has a more benign, less explored role as the brain professional phagocytes. Phagocytosis is a term coined from the Greek to describe the receptor-mediated engulfment and degradation of dead cells and microbes. In addition, microglia phagocytoses brain-specific cargo, such as axonal and myelin debris in spinal cord injury or multiple sclerosis, amyloid-beta deposits in Alzheimer's disease, and supernumerary synapses in postnatal development. Common mechanisms of recognition, engulfment, and degradation of the different types of cargo are assumed, but very little is known about the shared and specific molecules involved in the phagocytosis of each target by microglia. More importantly, the functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon, since it eliminates dead cells and induces an anti-inflammatory response. However, phagocytosis can also activate the respiratory burst, which produces toxic reactive oxygen species (ROS). Phagocytosis has been traditionally studied in pathological conditions, leading to the assumption that microglia have to be activated inorder to become efficient phagocytes. Recent data, however, has shown that unchallenged microglia phagocytose apoptotic cells during development and in adult neurogenic niches, suggesting an overlooked role in brain remodeling throughout the normal lifespan. The present review will summarize the current state of the literature regarding the role of microglial phagocytosis in maintaining tissue homeostasis in health as in disease.

Query-by-Example Spoken Term Detection ALBAYZIN 2012 evaluation: overview, systems, results, and discussion

Query-by-Example Spoken Term Detection (QbE STD) aims at retrieving data from a speech data repository given an acoustic query containing the term of interest as input. Nowadays, it has been receiving much interest due to the high volume of information stored in audio or audiovisual format. QbE STD differs from automatic speech recognition (ASR) and keyword spotting (KWS)/spoken term detection (STD) since ASR is interested in all the terms/words that appear in the speech signal and KWS/STD relies on a textual transcription of the search term to retrieve the speech data. This paper presents the systems submitted to the ALBAYZIN 2012 QbE STD evaluation held as a part of ALBAYZIN 2012 evaluation campaign within the context of the IberSPEECH 2012 Conference(a). The evaluation consists of retrieving the speech files that contain the input queries, indicating their start and end timestamps within the appropriate speech file. Evaluation is conducted on a Spanish spontaneous speech database containing a set of talks from MAVIR workshops(b), which amount at about 7 h of speech in total. We present the database metric systems submitted along with all results and some discussion. Four different research groups took part in the evaluation. Evaluation results show the difficulty of this task and the limited performance indicates there is still a lot of room for improvement. The best result is achieved by a dynamic time warping-based search over Gaussian posteriorgrams/posterior phoneme probabilities. This paper also compares the systems aiming at establishing the best technique dealing with that difficult task and looking for defining promising directions for this relatively novel task.

Calpain-Mediated Processing of Adenylate Cyclase Toxin Generates a Cytosolic Soluble Catalytically Active N-Terminal Domain

Bordetella pertussis, the whooping cough pathogen, secretes several virulence factors among which adenylate cyclase toxin (ACT) is essential for establishment of the disease in the respiratory tract. ACT weakens host defenses by suppressing important bactericidal activities of the phagocytic cells. Up to now, it was believed that cell intoxication by ACT was a consequence of the accumulation of abnormally high levels of cAMP, generated exclusively beneath the host plasma membrane by the toxin N-terminal catalytic adenylate cyclase (AC) domain, upon its direct translocation across the lipid bilayer. Here we show that host calpain, a calcium-dependent Cys-protease, is activated into the phagocytes by a toxin-triggered calcium rise, resulting in the proteolytic cleavage of the toxin N-terminal domain that releases a catalytically active "soluble AC''. The calpain-mediated ACT processing allows trafficking of the "soluble AC'' domain into subcellular organella. At least two strategic advantages arise from this singular toxin cleavage, enhancing the specificity of action, and simultaneously preventing an indiscriminate activation of cAMP effectors throughout the cell. The present study provides novel insights into the toxin mechanism of action, as the calpain-mediated toxin processing would confer ACT the capacity for a space- and time-coordinated production of different cAMP "pools'', which would play different roles in the cell pathophysiology.

Surface Expression and Subunit Specific Control of Steady Protein Levels by the Kv7.2 Helix A-B Linker

12 p.

Advances in Nonlinear Complexity Analysis for Partial Differential Equations

1 p. -- [Editorial Material]

Domain walls collision in Fe-rich and Co-rich glass covered microwires

JEMS 2012 - Joint European Magnetic Symposia edited by Tiberto, P; Affronte, M; Casoli, F; Fernandez, CD; Gubbiotti, G; Marquina, C; Pratt, F; Solzi, M; Tacchi, S; Vavassori, P. 6th Joint European Magnetic Symposia (JEMS) Parma, ITALY SEP 09-14, 2012

ICGE: an R package for detecting relevant clusters and atypical units in gene expression

Background: Gene expression technologies have opened up new ways to diagnose and treat cancer and other diseases. Clustering algorithms are a useful approach with which to analyze genome expression data. They attempt to partition the genes into groups exhibiting similar patterns of variation in expression level. An important problem associated with gene classification is to discern whether the clustering process can find a relevant partition as well as the identification of new genes classes. There are two key aspects to classification: the estimation of the number of clusters, and the decision as to whether a new unit (gene, tumor sample ... ) belongs to one of these previously identified clusters or to a new group. Results: ICGE is a user-friendly R package which provides many functions related to this problem: identify the number of clusters using mixed variables, usually found by applied biomedical researchers; detect whether the data have a cluster structure; identify whether a new unit belongs to one of the pre-identified clusters or to a novel group, and classify new units into the corresponding cluster. The functions in the ICGE package are accompanied by help files and easy examples to facilitate its use. Conclusions: We demonstrate the utility of ICGE by analyzing simulated and real data sets. The results show that ICGE could be very useful to a broad research community.

The locus coeruleus Is Directly Implicated in L-DOPA-Induced Dyskinesia in Parkinsonian Rats: An Electrophysiological and Behavioural Study

Despite being the most effective treatment for Parkinson's disease, L-DOPA causes a development of dyskinetic movements in the majority of treated patients. L-DOPA-induced dyskinesia is attributed to a dysregulated dopamine transmission within the basal ganglia, but serotonergic and noradrenergic systems are believed to play an important modulatory role. In this study, we have addressed the role of the locus coeruleus nucleus (LC) in a rat model of L-DOPA-induced dyskinesia. Single-unit extracellular recordings in vivo and behavioural and immunohistochemical approaches were applied in rats rendered dyskinetic by the destruction of the nigrostriatal dopamine neurons followed by chronic treatment with L-DOPA. The results showed that L-DOPA treatment reversed the change induced by 6-hydroxydopamine lesions on LC neuronal activity. The severity of the abnormal involuntary movements induced by L-DOPA correlated with the basal firing parameters of LC neuronal activity. Systemic administration of the LC-selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine did not modify axial, limb, and orolingual dyskinesia, whereas chemical destruction of the LC with ibotenic acid significantly increased the abnormal involuntary movement scores. These results are the first to demonstrate altered LC neuronal activity in 6-OHDA lesioned rats treated with L-DOPA, and indicate that an intact noradrenergic system may limit the severity of this movement disorder.