Learned helplessness in the rat: Effect of response topography in a within-subject design

Three experiments investigated learned helplessness in rats manipulating response topography within-subject and different intervals between treatment and tests among groups. In Experiment 1, rats previously exposed to inescapable shocks were tested under an escape contingency where either jumping or nose poking was required to terminate shocks: tests were run either 1, 14 or 28 days after treatment. Most rats failed to jump, as expected, but learned to nose poke, regardless of the interval between treatment and tests and order of testing. The same results were observed in male and female rats from a different laboratory (Experiment 2) and despite increased exposure to the escape contingencies using a within-subject design (Experiment 3). Furthermore, no evidence of helplessness reversal was observed, since animals failed to jump even after having learned to nose-poke in a previous test session. These results are not consistent with a learned helplessness hypothesis, which claims that shock (un)controllability is the key variable responsible for the effect. They are nonetheless consistent with the view that inescapable shocks enhance control by irrelevant features of the relationship between the environment and behavior. (C) 2010 Elsevier B.V. All rights reserved.

Dose-dependent effect of Resveratrol on bladder cancer cells: Chemoprevention and oxidative stress

Background: Over 6 million people die annually in the world because of cancer. Several groups are focused on studying cancer chemoprevention approaches. Resveratrol, a polyphenol, at high dosages, has been reported as antitumor and chemopreventive. However, it has a dose-dependent effect on cell death, even on some cancer cells. Objectives: Our aim was to investigate this dose-dependent effect on human bladder carcinoma ECV304 cells during oxidative stress condition. Methods: For this purpose. ECV304 cells incubated with different Resveratrol concentrations were analyzed as for their metabolic rate, membrane permeability, DNA fragmentation, anti/proapoptotic protein levels and phosphatidylserine exposure after oxidative stress. Results: Resveratrol induced cell death at high concentrations (>20 mu M), but not at low ones (0.1-20 mu M). Pretreatment with 2.5 mu M protected the cells from oxidative damage, whereas 50 mu M intensified the cell death and significantly increased Bad/Bcl-2 ratio (proapoptotic/antiapoptotic proteins). Resveratrol was able to modulate NO and PGE(2) secretion and performed an anti-adhesion activity of neutrophils on PMA-activated ECV304 cells. Conclusions: Resveratrol at high doses induces cell death of ECV304 cells whereas low doses induce protection. Modulation of Bcl-2 protein induced by Resveratrol could be mediating this effect. This information about the role of Resveratrol on cancer alerts us about its dose-dependent effects and could lead the design of future chemoprevention strategies. Published by Elsevier Ireland Ltd.

Effects of a CPT-even and Lorentz-violating nonminimal coupling on electron-positron scattering

We propose a new CPT-even and Lorentz-violating nonminimal coupling between fermions and Abelian gauge fields involving the CPT-even tensor (K-F)(mu nu alpha beta) of the standard model extension. We thus investigate its effects on the cross section of the electron-positron scattering by analyzing the process e(+) + e(-) -> mu(+) + mu(-). Such a study was performed for the parity-odd and parity-even nonbirefringent components of the Lorentz-violating (K-F)(mu nu alpha beta) tensor. Finally, by using experimental data available in the literature, we have imposed upper bounds as tight as 10(-12) (eV)(-1) on the magnitude of the CPT-even and Lorentz-violating parameters while nonminimally coupled. DOI: 10.1103/PhysRevD.86.125033

Proliferative Activity in Ischemia/Reperfusion Injury in Hepatectomized Mice: Effect of N-Acetylcysteine

Background. Dysfunction of the liver after transplantation may be related to the graft size and ischemia/reperfusion (I/R) injury. N-Acetylcysteine (NAC) exerts beneficial effects on livers undergoing ischemia reperfusion. We sought to evaluate NAC modulation on reduced livers associated with I/R injury. Methods. Male C57BL/6 mice of 8 weeks of age were divided into groups: 50% hepatectomy (G-Hep); NAC (G-Hep + NAC [150 mg/kg]) via vena cava 15 minutes before hepatectomy; ischemia (G-Hep + IR); NAC with hepatectomy (G-IR + Hep + Nac); and IR using 30 minutes selective hepatic occlusion and reperfusion for 24 hours. After 24 hours, the remaining liver was removed, for staining with hematoxylin and eosin or labeling by proliferating cell nuclear antigen. Blood was collected for biochemical evaluations. Significance was considered for P <= .05. Results. Aspartate aminotransferase was high in all studied groups reflecting the hepatectomy and intervention. injuries. However, when assessing alanine aminotransferase, which depicts liver function, induction of IR promoted a greater increase than hepatectomy (P = .0003). NAC decreased ALT activity in all groups, even in association with I/R (P < .05), reflecting a modulation of the injury. Necrosis resulting from IR was mitigated by NAC. The experimental model of 50% reduced live promoted regeneration of the hepatic remnant, which was accentuated by NAC, according to the total number of hepatocytes and PCNA values. Conclusion. NAC preserved the remnant liver in mice and stimulates regeneration even after IR injury.

Effect of Byrsonima crassa and Phenolic Constituents on Helicobacter pylori-Induced Neutrophils Oxidative Burst

Byrsonima crassa Niedenzu (Malpighiaceae) is used in Brazilian folk medicine for the treatment of diseases related mainly to gastric ulcers. In a previous study, our group described the gastric protective effect of the methanolic extract from the leaves of B. crassa. The present study was carried out to investigate the effects of methanolic extract and its phenolic compounds on the respiratory burst of neutrophils stimulated by H. pylori using a luminol-based chemiluminescence assay as well as their anti-H. pylori activity. The suppressive activity on oxidative burst of H. pylori-stimulated neutrophils was in the order of methyl gallate > (+)-catechin > methanol extract > quercetin 3-O-alpha-L-arabinopyranoside > quercetin 3-O-beta-D-galactopyranoside > amentoflavone. Methyl gallate, compound that induced the highest suppressive activity with IC50 value of 3.4 mu g/mL, did not show anti-H. pylori activity. B. crassa could be considered as a potential source of natural antioxidant in gastric ulcers by attenuating the effects on the damage to gastric mucosa caused by neutrophil generated reactive oxygen species, even when H. pylori displays its evasion mechanisms.

Nitrate reduces the negative effect of UV radiation on photosynthesis and pigmentation in Gracilaria tenuistipitata (Rhodophyta): the photoprotection role of mycosporine-like amino acids

Photoprotection of the agarophyte red alga Gracilaria tenuistipitata against ultraviolet radiation (UVR) was investigated in algae submitted for 1 week to photosynthetically active radiation (PAR, 260 mu mol photons m(-2) s(-1)) or PAR + UVR (UV-A, 8.13 W m(-2) and UV-B, 0.42 W m(-2)) under different nitrogen concentrations: 0, 0.1, and 0.5 mM of NO3-. Photosynthetic pigments decreased during the time of the experiment mainly under low nitrogen supply and UVR. Incubation under high nitrogen supply (0.5 mM) sustained the photosynthetic levels over time. In contrast, mycosporine-like amino acids (MAAs) increased up to eightfold in the presence of UVR and 0.5 mM NO3-. Under PAR + UVR, maximal quantum yield was positively correlated to MAA abundance, whereas under PAR no correlation was found. The photosynthetic yield of algae cultivated during seven days under PAR + UVR was less affected by a 30-min exposure of high UVR (16 W m(-2)) and fully recovered after transferring to low PAR irradiances, whereas algae kept under PAR were more affected by UV exposure and no full recovery was observed. Growth rates decreased after three days in the presence of UVR and under low nitrate supply. However, these rates were similar when compared with treatments of PAR and PAR + UVR after seven days, with the exception of samples in 0 mM NO3-, indicating that the acclimation after one week's exposure is related to nitrate supply. In conclusion, the lowest negative effect of UVR on photosynthesis and growth rate in high N-supply-grown algae could be explained by the stimulation of photoprotection mechanisms, such as accumulation of MAAs. Photostimulation of MAA accumulation by UVR under high N supply was observed in G. tenuistipitata even after 20 years in culture without the induction of this photomorphogenic light signal.

A Poisson mixed model with nonnormal random effect distribution

In this paper, we propose a random intercept Poisson model in which the random effect is assumed to follow a generalized log-gamma (GLG) distribution. This random effect accommodates (or captures) the overdispersion in the counts and induces within-cluster correlation. We derive the first two moments for the marginal distribution as well as the intraclass correlation. Even though numerical integration methods are, in general, required for deriving the marginal models, we obtain the multivariate negative binomial model from a particular parameter setting of the hierarchical model. An iterative process is derived for obtaining the maximum likelihood estimates for the parameters in the multivariate negative binomial model. Residual analysis is proposed and two applications with real data are given for illustration. (C) 2011 Elsevier B.V. All rights reserved.

Probing the cosmic distance-duality relation with the Sunyaev-Zel'dovich effect, X-ray observations and supernovae Ia

Context. The angular diameter distances toward galaxy clusters can be determined with measurements of Sunyaev-Zel'dovich effect and X-ray surface brightness combined with the validity of the distance-duality relation, D-L(z)(1 + z)(2)/D-A(z) = 1, where D-L(z) and D-A(z) are, respectively, the luminosity and angular diameter distances. This combination enables us to probe galaxy cluster physics or even to test the validity of the distance-duality relation itself. Aims. We explore these possibilities based on two different, but complementary approaches. Firstly, in order to constrain the possible galaxy cluster morphologies, the validity of the distance-duality relation (DD relation) is assumed in the Lambda CDM framework (WMAP7). Secondly, by adopting a cosmological-model-independent test, we directly confront the angular diameters from galaxy clusters with two supernovae Ia (SNe Ia) subsamples (carefully chosen to coincide with the cluster positions). The influence of the different SNe Ia light-curve fitters in the previous analysis are also discussed. Methods. We assumed that eta is a function of the redshift parametrized by two different relations: eta(z) = 1 +eta(0)z, and eta(z) = 1 + eta(0)z/(1 + z), where eta(0) is a constant parameter quantifying the possible departure from the strict validity of the DD relation. In order to determine the probability density function (PDF) of eta(0), we considered the angular diameter distances from galaxy clusters recently studied by two different groups by assuming elliptical and spherical isothermal beta models and spherical non-isothermal beta model. The strict validity of the DD relation will occur only if the maximum value of eta(0) PDF is centered on eta(0) = 0. Results. For both approaches we find that the elliptical beta model agrees with the distance-duality relation, whereas the non-isothermal spherical description is, in the best scenario, only marginally compatible. We find that the two-light curve fitters (SALT2 and MLCS2K2) present a statistically significant conflict, and a joint analysis involving the different approaches suggests that clusters are endowed with an elliptical geometry as previously assumed. Conclusions. The statistical analysis presented here provides new evidence that the true geometry of clusters is elliptical. In principle, it is remarkable that a local property such as the geometry of galaxy clusters might be constrained by a global argument like the one provided by the cosmological distance-duality relation.

Dual effect of Lutzomyia longipalpis saliva on Leishmania braziliensis infection is mediated by distinct saliva-induced cellular recruitment into BALB/c mice ear

Abstract Background Leishmania parasites are transmitted to their vertebrate hosts by infected Phlebotomine sand flies during the blood meal of the flies. Sand fly saliva is known to enhance Leishmania spp. infection, while pre-exposure to saliva protects mice against parasitic infections. In this study, we investigated the initial inflammatory leucocyte composition induced by one or three inocula of salivary gland extract (SGE) from Lutzomyia longipalpis in the presence or absence of Leishmania braziliensis. Results We demonstrated that inoculating SGE once (SGE-1X) or three times (SGE-3X), which represented a co-inoculation or a pre-exposure to saliva, respectively, resulted in different cellular infiltrate profiles. Whereas SGE-1X led to the recruitment of all leucocytes subtypes including CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils, the immune cell profile in the SGE-3X group differed dramatically, as CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils were decreased and CD8+ T cells were increased. The SGE-1X group did not show differences in the ear lesion size; however, the SGE-1X group harbored a higher number of parasites. On the other hand, the SGE-3X group demonstrated a protective effect against parasitic disease, as the parasite burden was lower even in the earlier stages of the infection, a period in which the SGE-1X group presented with larger and more severe lesions. These effects were also reflected in the cytokine profiles of both groups. Whereas the SGE-1X group presented with a substantial increase in IL-10 production, the SGE-3X group showed an increase in IFN-γ production in the draining lymph nodes. Analysis of the inflammatory cell populations present within the ear lesions, the SGE-1X group showed an increase in CD4+FOXP3+ cells, whereas the CD4+FOXP3+ population was reduced in the SGE-3X group. Moreover, CD4+ T cells and CD8+ T cells producing IFN-γ were highly detected in the ears of the SGE-3X mice prior to infection. In addition, upon treatment of SGE-3X mice with anti-IFN-γ monoclonal antibody, we observed a decrease in the protective effect of SGE-3X against L. braziliensis infection. Conclusions These results indicate that different inocula of Lutzomyia longipalpis salivary gland extract can markedly modify the cellular immune response, which is reflected in the pattern of susceptibility or resistance to Leishmania braziliensis infection.

Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.