Synthesis and conformational analysis of leptocarpin derivatives. Influence of modification of the oxirane ringon leptocarpin's cytotoxic activity.

Indexación: ScieloABSTRACT The reaction in acidconditions of Leptocarpin 1, a compound with antitumor activity, formed two new isomeric products, 8b-angeloyl-1b,3b-dihydroxy-4,10-dimethyl,-D11(13) methylen-4Z,9Z-dieneheliangol-6,12-olide 2 and 8b-angeloyl-1b,3b-dihydroxy-4-methyl-D11(13),D11(14)-dimethylen-4Z-eneheliangol-6,12-olide 3, whose structures reported in this study were established by spectroscopy (1H-NMR, 13C-NMR, MS and IR) and confirmedthrough ROESY experiments and theoretical studies by molecular mechanics. The in vitro cytotoxicity of these isomeric compounds was less active than leptocarpin, showing the importance of the oxirane ring in the biological activity. Cytotoxic activity was measured in six cancer cell lines. Keywords: Conformational analysis; Heliangolide; Sesquiterpene lactones; Cytotoxicity

An unidentified TeV source in the vicinity of Cygnus OB2

Deep observation (∼113 hrs) of the Cygnus region at TeV energies using the HEGRA stereoscopic system of air Čerenkov telescopes has serendipitously revealed a signal positionally inside the core of the OB association Cygnus OB2, at the edge of the 95% error circle of the EGRET source 3EG J2033+4118, and ∼0.5° north of Cyg X-3. The source centre of gravity is RA αJ2000: 20hr32m07s± 9.2stats±2.2syss, Dec δJ2000: +41°30′30″2.0stat±0.4′sys. The source is steady, has a post-trial significance of +4.6σ, indication for extension with radius 5.6′ at the ∼3σ level, and has a differential power-law flux with hard photon index of - 1.9 ± 0.3stat ± 0.3sys. The integral flux above 1 TeV amounts ∼3% that of the Crab. No counterpart for the TeV source at other wavelengths is presently identified, and its extension would disfavour an exclusive pulsar or AGN origin. If associated with Cygnus OB2, this dense concentration of young, massive stars provides an environment conducive to multi-TeV particle acceleration and likely subsequent interaction with a nearby gas cloud. Alternatively, one could envisage γ-ray production via a jet-driven termination shock.F. A. Aharonian, ... G. P. Rowell, ... [et al

Cadmium and/or copper excess induce interdependent metal accumulation, DNA methylation, induction of metal chelators and antioxidant defences in the seagrass Zostera marina

In this investigation, we assessed the effects of Cu and/or Cd excess on physiological and metabolic processes of the widespread seagrass Zostera marina. Adult were exposed to low Cd and Cu (0.89 and 0.8 µM, respectively) and high Cd and Cu (8.9 and 2.4 µM, respectively) for 6 d at: Control conditions; low Cu; high Cu; low Cd; high Cd; low Cd and low Cu; and high Cd and high Cu. Photosynthetic performance decreased under single and combined treatments, although effects were more negative under Cu than Cd. Total Cu accumulation was higher than Cd, under single and combined treatments; however, their accumulation was generally lower when applied together, suggesting competition among them. Levels of glutathione (GSH) and phytochelatins (PCs) followed patterns similar to metal accumulation, with up to PC5, displaying adaptations in tolerance. A metallothionein (MET) gene showed upregulation only at high Cd, low Cu, and high Cu. The expression of the enzymes glutathione reductase (GR), ascorbate peroxidase (APX), and catalase (CAT) was greatest at high Cu, and at high Cd and Cu together; the highest expression was under Cu, alone and combined. Both metals induced upregulation of the DNA methyltransferases CMT3 and DRM2, with the highest expression at single Cu. The DNA demethylation ROS1 was overexpressed in treatments containing high Cu, suggesting epigenetic modifications. The results show that under copper and/or cadmium, Z. marina was still biologically viable; certainly based, at least in part, on the induction of metal chelators, antioxidant defences and methylation/demethylation pathways of gene regulation

Lagrangean relaxation for the capacitated hub location problem . . .

This paper considers the Capacitated Hub Location Problem with Single Assignment. We propose a Lagrangean Relaxation to obtain tight upper and lower bounds. The lagrangean function that we formulate exploits the structure of the problem and can be decomposed into smaller subproblems that can be solved efficiently. In addition, we present some simple reduction tests, based on the lagrangean relaxation bounds, that allows us to reduce considerably the size of the formulation and thus, to reduce the computational effort. Computational experiments have been performed with both benchmark instances from literature and with some new lager instances. The obtained results are remarkable. For all tested instances (ranging from 10 to 200 nodes) we obtain or improve the best known solution and the obtained duality gaps, between our upper and lower bounds, never exceed 3.4%

Personal identity: an issue that demands revision in today’s philosophical and interdisciplinary dialogue

Today we are witnessing an unprecedented crisis caused by the Covid-19 pandemic. Its unparalleled and unpredictable character, added to its expansion and the way it has affected contemporary society, also emphasizes the underlying question, who are we? Why and in what sense? In the current context, where, on the one hand, there is a loss of confidence in the ways in which we govern ourselves, as well as an uncertainty regarding the direction that this crisis may take and the threshold to which it can lead us, the question certainly arises as to whether what we are has a background on which to support ourselves; if anything, that "who" that we claim to be and to whom we bear witness in our work can withstand the test of the unpredictable and unexpected, of what has plunged us into a situation as unusual as it is incomprehensible. As tragic as this situation affects us worldwide, it affects us both collectively and personally. With all the momentum with which this even strikes us, do we not live it precisely as a challenge to the security whereby we usually respond to the question of our personal identity? Is it not at such an exceptional moment as this, when the question of personal identity worries us greatly as soon as our temporal condition takes on real importance, which, irreversible as such, offers us in turn the opportunity to reverse the situation we are involved in? Is it not during this worldwide crisis, which we first experienced as a personal rupture, which in turn gives us the opportunity to appreciate the tension we live in, but which is present, however, most of the time, invisible to us, namely, that of being engaged in a habitual, inhabited space, consolidated by a sense that we inherit, at the same time that we believe we are called to innovate on that? Isn't this time the one that certainly makes history in our personal and social fabric? However, it seems that we also can, in an unprecedented way, experience this crisis as an identity crisis insofar as it enhances its problematic dimension. The articles we present here have the quality of confronting this question from multiple perspectives that, irreducible between them, still manage to give certain lucidity to that which we comprehend around the question of “who am I?, which is especially necessary at this moment. In this sense, the texts put us, in one hand, on the phenomenological-eventual scope just like it has been elaborated by the French thinker, Claude Romano, who interrogates the human being in his capacity to embrace the events that shock the subject’s existencial unfolding. On the other hand, we have collected articles that revolve around the hermeneutic phenomenology of Paul Ricœur, focusing their attention both on the ontological condition of human beings, as well as on the perspective of his hermeneutics of action and narrative. We finally conclude with a text by Shaumann which questions the relationship between identity and alienation, interrogating the philosophies of Paul Ricœur and Martin Heidegger

AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors

YesAlternative splicing of pre-mRNAs significantly contributes to the complexity of gene expression in higher organisms, but the regulation of the splice site selection remains incompletely understood. We have previously demonstrated that a chromatin-associated protein, AKAP95 (AKAP8), has a remarkable activity in enhancing chromatin transcription. In this study, we have shown that AKAP95 physically interacts with many factors involved in transcription and RNA processing, and functionally regulates pre-mRNA splicing. AKAP95 directly promotes splicing in vitro and the inclusion of a specific exon of an endogenous gene FAM126A. The N-terminal YG-rich domain of AKAP95 is important for its binding to RNA processing factors including selective groups of hnRNP proteins, and its zinc finger domains are critical for pre-mRNA binding. Genome-wide binding assays revealed that AKAP95 bound preferentially to proximal intronic regions on a large number of pre-mRNAs in human transcriptome, and AKAP95 depletion predominantly resulted in reduced inclusion of many exons. AKAP95 also selectively coordinates with hnRNP H/F and U proteins in regulating alternative splicing events. We have further shown that AKAP95 directly interacts with itself. Taken together, our results establish AKAP95 as a novel and mostly positive regulator of premRNA splicing and a possible integrator of transcription and splicing regulation, and support a model that AKAP95 facilitates the splice site communication by looping out introns through both RNA-binding and protein-protein interaction.This work was supported by a UAB start-up fund to H.J

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

Peer reviewe

Validation and comparison of instruments to identify frail patientes in primary care settings: Study protocol

Background: In the last few years several indices and tools, aimed at identifying frail subjects in various care settings have been developed. However, to date none of them has been incorporated into usual practice in the primary care setting. The purposes of this study are: 1) to evaluate the predictive capacity of the Tilburg Frailty Indicator (TFI), the Gérontopôle Frailty Screening Tool (GFST) and the KoS model together with two biomarker levels (SOX2 and p16INK4a) for adverse events related to frailty; 2) to determine differences in the use of healthcare services according to frailty. Methods/design: Prospective multicentre cohort study with a 2-year follow-up. The study will be performed in primary care centres of Gipuzkoa and Costa del Sol, both located in Spain. Autonomous, non-institutionalized individuals aged 70 and over that agree to participate in this study will constitute the study population. A total of 900 individuals will be randomly selected from the healthcare administrative data bases of the participating health services. Data will be collected at baseline and at 1 and 2 years. The main independent variables assessed at baseline will be TFI outcomes, GFST and the KoS model, together with the expression of SOX2 and p16INK4a levels. During follow-up, loss of autonomy, the occurrence of death and consumption of healthcare resources will be assessed. Discussion: The main focus of this work is the identification and evaluation of several instruments constructed under different rationales to identify frail subjects in primary care settings. The resulting outcomes have potential for direct application to the primary care practice. Early identification of the onset of functional impairment of elderly is an essential, still unresolved aspect in the prevention of dependence in the scope of primary care

Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

Peer reviewe