Short asymmetric synthesis of phenanthroindolizidines through chiral homoallylic sulfinamine

An efficient stereocontrolled preparation of chiral phenanthroindolizidines is detailed. The synthesis relies on the stereoselective indium-mediated allylation of 2-(phenanthren-9-yl)acetaldehyde derivatives with chiral tert-butylsulfinamide. Chemoselective transformations from the corresponding homoallylic sulfinamine allow the synthesis of the phenanthroindolizidines in only three synthetic operations, without any detectable racemization. Following this procedure, the synthesis of natural (−)-tylophorine was successfully accomplished.We thank the Spanish Ministerio de Ciencia e Innovación for their financial support (CTQ2011-24165). C. A.-T. thanks the ISO for a grant

Alternative method for the metrological characterization of spur gears in the sub-millimeter range using optical equipment

The aim of this work is to develop a software that allows the inspection of spur gear manufactured in the sub-millimeter range. The measurements are made using a digital optical machine and using an analysis proprietary software implemented in Matlab®, which is able to handle images, captured using the digital optical machine. The software allows to evaluate the profile and pitch deviations as establish in the ISO/TR 10064-1:1992 standar

A radical addition/cyclization of diverse ethers to 2-isocyanobiaryls under mildly basic aqueous conditions

Mildly basic aqueous conditions facilitated the tert-butyl peroxybenzoate (TBPB) mediated dehydrogenative addition of a range of ethers, including acetals, to diverse substituted 2-isocyanobiaryls. Mechanistic studies suggest that this radical cascade is an example of base promoted homolytic aromatic substitution (BHAS).We thank the Ministerio de Economia y Competitividad (CTQ2015-66624-P) and the University of Alicante (VIGROB-173) for financial support. C. A.-T. thanks the ISO for a grant

Concise asymmetric syntheses of novel phenanthroquinolizidines

The first preparation of enantioenriched phenanthroquinolizidines with a quaternary center at C14a was accomplished in seven steps from readily available starting materials. Key steps were an efficient dynamic kinetic allylation of a diastereomeric mixture of chiral tert-butylsulfinyl ketimines and the construction of a piperidine E ring by rhodium catalyzed hydroformylation. The Stevens rearrangement of the corresponding N-benzyl derivatives took place smoothly, allowing the installation of a benzyl moiety at C9 in a trans relationship with the methyl group. The cytoxicity of the prepared phenanthroquinolizidines was evaluated against different human cancer cell lines.We thank the Spanish Ministerio de Ciencia e Innovación (CTQ2011-24165) and the University of Alicante (VIGROB-173) for financial support. C. A.-T. thanks the ISO for a grant

Influence of pH and CO2 source on the performance of microalgae-based secondary domestic wastewater treatment in outdoors pilot raceways.

Influence of pH and CO2 source on the performance of microalgae-based secondary domestic wastewater treatment in outdoors pilot raceway

Emerging Perspectives on Gene Therapy Delivery for Neurodegenerative and Neuromuscular Disorders.

Neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD) and Parkinson's Disease (PD), are a group of heterogeneous diseases that mainly affect central nervous system (CNS) functions. A subset of NDDs exhibit CNS dysfunction and muscle degeneration, as observed in Gangliosidosis 1 (GM1) and late stages of PD. Neuromuscular disorders (NMDs) are a group of diseases in which patients show primary progressive muscle weaknesses, including Duchenne Muscular Dystrophy (DMD), Pompe disease, and Spinal Muscular Atrophy (SMA). NDDs and NMDs typically have a genetic component, which affects the physiological functioning of critical cellular processes, leading to pathogenesis. Currently, there is no cure or efficient treatment for most of these diseases. More than 200 clinical trials have been completed or are currently underway in order to establish safety, tolerability, and efficacy of promising gene therapy approaches. Thus, gene therapy-based therapeutics, including viral or non-viral delivery, are very appealing for the treatment of NDDs and NMDs. In particular, adeno-associated viral vectors (AAV) are an attractive option for gene therapy for NDDs and NMDs. However, limitations have been identified after systemic delivery, including the suboptimal capacity of these therapies to traverse the blood-brain barrier (BBB), degradation of the particles during the delivery, high reactivity of the patient's immune system during the treatment, and the potential need for redosing. To circumvent these limitations, several preclinical and clinical studies have suggested intrathecal (IT) delivery to target the CNS and peripheral organs via cerebrospinal fluid (CSF). CSF administration can vastly improve the delivery of small molecules and drugs to the brain and spinal cord as compared to systemic delivery. Here, we review AAV biology and vector design elements, different therapeutic routes of administration, and highlight CSF delivery as an attractive route of administration. We discuss the different aspects of neuromuscular and neurodegenerative diseases, such as pathogenesis, the landscape of mutations, and the biological processes associated with the disease. We also describe the hallmarks of NDDs and NMDs as well as discuss current therapeutic approaches and clinical progress in viral and non-viral gene therapy and enzyme replacement strategies for those diseases

A proposal for the metrological characterization of circular features with digital optical machines

This paper aims to analyze the different adjustment methods commonly used to characterize indirect metrology circular features: least square circle, minimum zone circle, maximum inscribed circle and minimum circumscribed circle. The analysis was performed from images obtained by digital optical machines. The calculation algorithms, self-developed, have been implemented in Matlab® and take into consideration as study variables: the amplitude of angular sector of the circular feature, its nominal radio and the magnification used by the optical machine. Under different conditions, it was determined the radius and circularity error of different circular standards. The comparison of the results, obtained by the different methods of adjustments used, with certified values for the standards, has allowed us to determine the accuracy of each method and its scope

Syntheses and Cytotoxicity of (R)- and (S)-7-Methoxycryptopleurine

Two efficient protocols are described for the transformation of a key chiral homoallyllic sulfinamine intermediate in four steps into enantioenriched 7-methoxycryptopleurine. While one of the protocols relied on a rhodium catalyzed linear hydroformylation process, the alternative approach was based on a ring-closing metathesis from the corresponding N-allyl-sulfinamine. The cytotoxic evaluation of both enantiomers of the target compound demonstrated that the (R)-compound is much more potent than its antipode against the four cancer cell lines examined.We thank the Spanish Ministerio de Ciencia e Innovación (CTQ2011-24165) for financial support. I.B. acknowledges the Generalitat Valenciana for a postdoctoral fellowship (ACIF/2011/159). C.A.-T. thanks the ISO for a grant

TNFR1 signaling contributes to T cell anergy during staphylococcus aureus sepsis

Early research on sepsis has focused on the initial hyper-inflammatory, cytokine mediated phase of the disorder whereas the events that govern the concomitant and subsequent anti-inflammatory compensatory response are not completely understood. In this context, the putative participation of TNFR1-mediated signaling in the immunosuppressive phase of Staphylococcus aureus sepsis has not been elucidated. The aim of this study was to determine the role of TNFR1 in directing the immune dysfunction during S. aureus sepsis and the potential contribution of MDSC to this process. Using a model of sepsis of peritoneal origin and tnfr1 -/- mice, we demonstrated that during staphylococcal sepsis CD4 + T cell anergy is significantly dependent on TNFR1 expression and that signaling through this receptor has an impact on bacterial clearance in the spleen. MDSC played a major role in the generation of anergic CD4 + T cells and their accumulation in the spleen during S. aureus sepsis correlated with IL-6 induction. Although TNFR1 signaling was not required for MDSC accumulation and expansion in the spleen, it determined the in vivo expression of Arginase 1 and iNOS, enzymes known to participate in the suppressive function of this population. Moreover, our data indicate that TNFR1-mediated IL-10 production may modulate MDSC function during staphylococcal sepsis. Taken together these results indicate that TNFR1 plays a critical role on T cell dysfunction during S. aureus sepsis by regulating immunomodulatory mediators in MDSC. The role of TNFR1-mediated signaling during the immunosuppressive phase of staphylococcal sepsis should be considered when designing novel alternative therapeutic approaches.Fil: Ledo, Camila. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Gonzalez, Cintia Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Poncini, Carolina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Mollerach, Marta Eugenia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Marisa Ines. Universidad Maimónides; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

Unsaturated fatty acid intake during periconception and incidence of achieving pregnancy: a systematic review and meta-analysis

Background: Previous studies suggest that maternal diets enriched in unsaturated fatty acids may have a positive effect on pregnancy success. The aim of the present study was to conduct a systematic review and meta-analysis to evaluate whether increased dietary intake of polyunsaturated fatty acids (PUFAs) or monounsaturated fatty acids (MUFAs) during the periconception period has beneficial effects on the achievement of pregnancy in women. Methods: The electronic databases PubMed, Medline and Cochrane Central Register, as well as references in related review articles, were searched to find studies assessing the effects of unsaturated fatty acid dietary intake during the periconception period on the achievement of pregnancy in women. Pregnancy was confirmed by high levels of hCG (biochemical means) and ultrasound confirmation of a gestational sac and heartbeat (clinical means). Results: For the meta-analysis evaluating the effects of periconceptional diets enriched in PUFAs on pregnancy, four articles, providing data on 2,121 patients, were included. Results showed that periconceptional intake of PUFAs has no significant effects on achieving pregnancy compared to controls, according to both the fixed effects and random effects models (RR = 0.99, 95% CI 0.98–1.00). Further secondary analysis considering ω-6 and ω-3 PUFAs separately showed no significant effects on achieving pregnancy compared to controls. On the other hand, for the meta-analysis evaluating the effects of periconceptional diets enriched in MUFAs on achieving pregnancy, five articles, providing data on 2,473 patients, were included. Results showed that periconceptional dietary intake of MUFAs has significant effects on achieving pregnancy compared to controls according to the fixed effects model (RR = 1.03, 95% CI 1.01–1.06, p < 0.02) but not to the random effects model, due to heterogeneity. A secondary meta-analysis excluding one study which led to heterogeneity showed significant effects of MUFAs on achieving pregnancy compared to controls, according to both the fixed effects and random effects models (RR = 1.03, 95% CI 1.01–1.05, p < 0.02). Conclusion: The meta-analysis of published clinical studies suggests that diets enriched in MUFAs, although not those enriched in PUFAs, may have a positive effect on pregnancy success as determined by HCG and ultrasonography.Fil: Gatti, Cintia Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Gomez Ribot, Dalmiro Leonardo Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Mariani, Nestor Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin