Oxidative stress specifically downregulates survivin to promote breast tumour formation.

BackgroundBreast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood.ResultsDETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours.ConclusionOur data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation

The Role of Δ(1232)\Delta(1232) in Two-pion Exchange Three-nucleon Potential

In this paper we have studied the two-pion exchange three-nucleon potential $(2\pi E-3NP)$ using an approximate $SU(2) \times SU(2)$ chiral symmetry of the strong interaction. The off-shell pion-nucleon scattering amplitudes obtained from the Weinberg Lagangian are supplemented with contributions from the well-known $\sigma$-term and the $\Delta(1232)$ exchange. It is the role of the $\Delta$-resonance in $2\pi E-3NP$, which we have investigated in detail in the framework of the Lagrangian field theory. The $\Delta$-contribution is quite appreciable and, more significantly, it is dependent on a parameter Z which is arbitrary but has the empirical bounds $|Z| \leq 1/2$. We find that the $\Delta$-contribution to the important parameters of the $2\pi E-3NP$ depends on the choice of a value for Z, although the correction to the binding energy of triton is not expected to be very sensitive to the variation of Z within its bounds.Comment: 14 pages, LaTe

Semileptonic Decays of Heavy Lambda Baryons in a Quark Model

The semileptonic decays of Lambda_c and Lambda_b are treated in the framework of a constituent quark model. Both nonrelativistic and semirelativistic Hamiltonians are used to obtain the baryon wave functions from a fit to the spectra, and the wave functions are expanded in both the harmonic oscillator and Sturmian bases. The latter basis leads to form factors in which the kinematic dependence on q^2 is in the form of multipoles, and the resulting form factors fall faster as a function of q^2 in the available kinematic ranges. As a result, decay rates obtained in the two models using the Sturmian basis are significantly smaller than those obtained using the harmonic oscillator basis. In the case of the Lambda_c, decay rates calculated using the Sturmian basis are closer to the experimentally reported rates. However, we find a semileptonic branching fraction for the Lambda_c to decay to excited Lambda* states of 11% to 19%, in contradiction with what is assumed in available experimental analyses. Our prediction for the Lambda_b semileptonic decays is that decays to the ground state Lambda_c provide a little less than 70% of the total semileptonic decay rate. For the decays Lambda_b to Lambda_c, the analytic form factors we obtain satisfy the relations expected from heavy-quark effective theory at the non-recoil point, at leading and next-to-leading orders in the heavy-quark expansion. In addition, some features of the heavy-quark limit are shown to naturally persist as the mass of the heavy quark in the daughter baryon is decreased.Comment: 51 pages, 8 figures, submitted to Physical Review

Recent models for adaptive personality differences: a review

In this paper we review recent models that provide adaptive explanations for animal personalities: individual differences in behaviour (or suites of correlated behaviours) that are consistent over time or contexts. We start by briefly discussing patterns of variation in behaviour that have been documented in natural populations. In the main part of the paper we discuss models for personality differences that (i) explain animal personalities as adaptive behavioural responses to differences in state, (ii) investigate how feedbacks between state and behaviour can stabilize initial differences among individuals and (iii) provide adaptive explanations for animal personalities that are not based on state differences. Throughout, we focus on two basic questions. First, what is the basic conceptual idea underlying the model? Second, what are the key assumptions and predictions of the model? We conclude by discussing empirical features of personalities that have not yet been addressed by formal modelling. While this paper is primarily intended to guide empiricists through current adaptive theory, thereby stimulating empirical tests of these models, we hope it also inspires theoreticians to address aspects of personalities that have received little attention up to now

LCrowdV: Generating Labeled Videos for Simulation-based Crowd Behavior Learning

We present a novel procedural framework to generate an arbitrary number of labeled crowd videos (LCrowdV). The resulting crowd video datasets are used to design accurate algorithms or training models for crowded scene understanding. Our overall approach is composed of two components: a procedural simulation framework for generating crowd movements and behaviors, and a procedural rendering framework to generate different videos or images. Each video or image is automatically labeled based on the environment, number of pedestrians, density, behavior, flow, lighting conditions, viewpoint, noise, etc. Furthermore, we can increase the realism by combining synthetically-generated behaviors with real-world background videos. We demonstrate the benefits of LCrowdV over prior lableled crowd datasets by improving the accuracy of pedestrian detection and crowd behavior classification algorithms. LCrowdV would be released on the WWW

Attitudes towards code-switching among adult mono- and multilingual language users

The present study investigates inter-individual variation (linked to personality traits, multilingualism and sociobiographical variables) in attitudes towards code-switching (CS) among 2070 multilinguals. Data were collected through an on-line questionnaire. We found that high levels of Tolerance of Ambiguity and Cognitive Empathy, and low levels of Neuroticism are linked with significantly more positive attitudes towards CS. Knowing many languages had a marginally positive effect. A more fine-grained analysis revealed that participants with mid-range global proficiency values were less positive towards CS than those at the lower and higher end of the scale. Participants who grew up in a bilingual family and in an ethnically diverse environment, and currently worked in an ethnically diverse environment had significantly more positive attitudes towards CS. Female participants and those with the lowest and highest levels of education appreciated CS most, and participants in their teens and twenties appreciated CS less than older participants. The findings thus show that the attitudes towards CS are linked to personality, language learning history and current linguistic practices, as well as some sociobiographical variables

Determination of the primary structure and carboxyl pKAs of heparin-derived oligosaccharides by band-selective homonuclear-decoupled two-dimensional 1H NMR

Determination of the structure of heparin-derived oligosaccharides by 1H NMR is challenging because resonances for all but the anomeric protons cover less than 2 ppm. By taking advantage of increased dispersion of resonances for the anomeric H1 protons at low pD and the superior resolution of band-selective, homonuclear-decoupled (BASHD) two-dimensional 1H NMR, the primary structure of the heparin-derived octasaccharide ∆UA(2S)-[(1 → 4)-GlcNS(6S)-(1 → 4)-IdoA(2S)-]3-(1 → 4)-GlcNS(6S) has been determined, where ∆UA(2S) is 2-O-sulfated ∆4,5-unsaturated uronic acid, GlcNS(6S) is 6-O-sulfated, N-sulfated β-d-glucosamine and IdoA(2S) is 2-O-sulfated α-l-iduronic acid. The spectrum was assigned, and the sites of N- and O-sulfation and the conformation of each uronic acid residue were established, with chemical shift data obtained from BASHD-TOCSY spectra, while the sequence of the monosaccharide residues in the octasaccharide was determined from inter-residue NOEs in BASHD-NOESY spectra. Acid dissociation constants were determined for each carboxylic acid group of the octasaccharide, as well as for related tetra- and hexasaccharides, from chemical shift–pD titration curves. Chemical shift–pD titration curves were obtained for each carboxylic acid group from sub-spectra taken from BASHD-TOCSY spectra that were measured as a function of pD. The pKAs of the carboxylic acid groups of the ∆UA(2S) residues are less than those of the IdoA(2S) residues, and the pKAs of the carboxylic acid groups of the IdoA(2S) residues for a given oligosaccharide are similar in magnitude. Relative acidities of the carboxylic acid groups of each oligosaccharide were calculated from chemical shift data by a pH-independent method

The link between foreign language classroom anxiety and psychoticism, extraversion, and neuroticism among adult bi- and multilinguals

The present study focuses on the link between three global personality traits (Psychoticism, Extraversion, and Neuroticism), one sociobiographical factor (knowledge of languages) and levels of foreign language classroom anxiety (FLCA) (Horwitz et al., 1986) in the second (L2), third (L3) and fourth (L4) language of two groups of adult language learners and users. The first group consisted of 86 students who were enrolled at Birkbeck College, University of London, UK and the second group consisted of 62 students from University of Les Illes Balears in Mallorca, Spain. The main aim was to check whether FLCA is unrelated to a basic personality trait reflecting anxiety (Neuroticism), as is generally reported in the Second Language Acquisition literature. Correlation analyses revealed that Neuroticism has a significant link with FLCA in the foreign languages of both groups, sharing between 9% and 25% of variance. Moderately significant relationships were found between Psychoticism, Extraversion and FLCA in one group only. Language knowledge had an effect on FLCA in some languages. Strong correlations between FLCA values in L2, L3 and L4, suggest that levels of FLCA are relatively stable across the foreign languages known by the learners/users

Nitric Oxide Induces Cell Death by Regulating Anti-Apoptotic BCL-2 Family Members

Nitric oxide (NO) activates the intrinsic apoptotic pathway to induce cell death. However, the mechanism by which this pathway is activated in cells exposed to NO is not known. Here we report that BAX and BAK are activated by NO and that cytochrome c is released from the mitochondria. Cells deficient in Bax and Bak or Caspase-9 are completely protected from NO-induced cell death. The individual loss of the BH3-only proteins, Bim, Bid, Puma, Bad or Noxa, or Bid knockdown in Bim−/−/Puma−/− MEFs, does not prevent NO-induced cell death. Our data show that the anti-apoptotic protein MCL-1 undergoes ASK1-JNK1 mediated degradation upon exposure to NO, and that cells deficient in either Ask1 or Jnk1 are protected against NO-induced cell death. NO can inhibit the mitochondrial electron transport chain resulting in an increase in superoxide generation and peroxynitrite formation. However, scavengers of ROS or peroxynitrite do not prevent NO-induced cell death. Collectively, these data indicate that NO degrades MCL-1 through the ASK1-JNK1 axis to induce BAX/BAK-dependent cell death