Vasopressinergic modulation of stress responses in the central amygdala of the Roman high-avoidance and low-avoidance rat

The central nucleus of the amygdala (CEA) is selectively involved in the passive component of the behavioral (immobility) and the accompanying parasympathetic response during conditioned, stressful environmental challenges. Vasopressinergic mechanisms in the brain seem to play a role in these stress responses. The effects of the neuropeptides arginine-8-vasopressin (AVP) and oxytocin (OXT) on modulating CEA activity during conditioned stress of inescapable footshock were studied in male Roman high-avoidance (RHA/Verh) and low-avoidance (RLA/Verh) rats, psychogenetically selected on the basis of shuttle-box acquisition behavior. In RLA/Verh rats, the cardiac and behavioral responses to the conditioned emotional stressor were bradycardia and immobility, suggesting an important role for the CEA in these rats. The RHA/Verh rats, however, failed to show any change in heart rate or immobility in response to a conditioned stress situation. The low dose of AVP (20 pg) in the CEA of conscious RLA/Verh rats caused an enhancement of the stress-induced bradycardiac and immobility response. However, the high dose of AVP (2 ng) and OXT (200 pg) attenuated the bradycardiac and immobility responses in the RLA/Verh rats. Infusion of AVP and OXT in the RHA/Verh rats failed to induce any change in heart rate nr immobility. Binding studies revealed that the AVP receptor selectively binds AVP with high affinity. In contrast, the OXT receptor recognizes both AVP and OXT with a similar (but lower) affinity. This suggests that the behavioral and autonomic responses of the high dose of AVP may be caused by OXT receptor stimulation. In conclusion, on the basis of the present results one may hypothesize that CEA differences in AVP and OXT innervation and/or receptor densities may contribute to the differences in coping strategy found in these animals.

Competing endogenous rna networks as biomarkers in neurodegenerative diseases

Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases

Parabolic stable surfaces with constant mean curvature

We prove that if u is a bounded smooth function in the kernel of a nonnegative Schrodinger operator $-L=-(\Delta +q)$ on a parabolic Riemannian manifold M, then u is either identically zero or it has no zeros on M, and the linear space of such functions is 1-dimensional. We obtain consequences for orientable, complete stable surfaces with constant mean curvature $H\in\mathbb{R}$ in homogeneous spaces $\mathbb{E}(\kappa,\tau)$ with four dimensional isometry group. For instance, if M is an orientable, parabolic, complete immersed surface with constant mean curvature H in $\mathbb{H}^2\times\mathbb{R}$, then $|H|\leq 1/2$ and if equality holds, then M is either an entire graph or a vertical horocylinder.Comment: 15 pages, 1 figure. Minor changes have been incorporated (exchange finite capacity by parabolicity, and simplify the proof of Theorem 1)

Recent developments in monitoring and modelling airborne pollen, a review

Public awareness of the rising importance of allergies and other respiratory diseases has led to increased scientific effort to accurately and rapidly monitor and predict pollen, fungal spores and other bioaerosols in our atmosphere. An important driving force for the increased social and scientific concern is the realisation that climate change will increasingly have an impact on worldwide bioaerosol distributions and subsequent human health. In this review we examine new developments in monitoring of atmospheric pollen as well as observation and source-orientated modelling techniques. The results of a Scopus® search for scientific publications conducted with the terms ‘Pollen allergy’ and ‘Pollen forecast’ included in the title, abstract or keywords show that the number of such articles published has increased year on year. The 12 most important allergenic pollen taxa in Europe as defined by COST Action ES0603 were ranked in terms of the most ‘popular’ for model-based forecasting and for forecasting method used. Betula, Poaceae and Ambrosia are the most forecast taxa. Traditional regression and phenological models (including temperature sum and chilling models) are the most used modelling methods, but it is notable that there are a large number of new modelling techniques being explored. In particular, it appears that Machine Learning techniques have become more popular and led to better results than more traditional observation-orientated models such as regression and time-series analyses

Mitogen-Activated Protein Kinase Phosphatase-1 Is Overexpressed in Non-Small Cell Lung Cancer and Is an Independent Predictor of Outcome in Patients

An increase in the activity of the mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vitro and in vivo. A key regulatory mechanism of the MAPKs [extracellular signal-regulated kinase (ERK); c-jun NH(2)-terminal kinase (JNK); and p38] is the dual specificity phosphatase CL100, also called MAPK phosphatase-1 (MKP-1). This study was designed to examine the involvement of CL100/MKP-1 and stress-related MAPKs in lung cancer. EXPERIMENTAL DESIGN: We assessed the expression of CL100/MKP-1 and the activation of the MAPKs in a panel of 18 human cell lines [1 primary normal bronchial epithelium, 8 non-small cell lung cancer (NSCLC), 7 small cell lung cancer (SCLC), and 2 carcinoids] and in 108 NSCLC surgical specimens. RESULTS: In the cell lines, CL100/MKP-1 expression was substantially higher in NSCLC than in SCLC. P-ERK, P-JNK, and P-p38 were activated in SCLC and NSCLC, but the degree of their activation was variable. Immunohistochemistry in NSCLC resection specimens showed high levels of CL100/MKP-1 and activation of the three MAPK compared with normal lung. In univariate analysis, no relationship was found among CL100/MKP-1 expression and P-ERK, P-JNK, or P-p38. Interestingly, high CL100/MKP-1 expression levels independently predicted improved survival in multivariate analysis. JNK activation associated with T(1-2) and early stage, whereas ERK activation correlated with late stages and higher T and N. Neither JNK nor ERK activation were independent prognostic factors when studied for patient survival. CONCLUSIONS: Our data indicate the relevance of MAPKs and CL100/MKP-1 in lung cancer and point at CL100/MKP-1 as a potential positive prognostic factor in NSCLC. Finally, our study supports the search of new molecular targets for lung cancer therapy within the MAPK signaling pathway

Configuration Complexities of Hydrogenic Atoms

The Fisher-Shannon and Cramer-Rao information measures, and the LMC-like or shape complexity (i.e., the disequilibrium times the Shannon entropic power) of hydrogenic stationary states are investigated in both position and momentum spaces. First, it is shown that not only the Fisher information and the variance (then, the Cramer-Rao measure) but also the disequilibrium associated to the quantum-mechanical probability density can be explicitly expressed in terms of the three quantum numbers (n, l, m) of the corresponding state. Second, the three composite measures mentioned above are analytically, numerically and physically discussed for both ground and excited states. It is observed, in particular, that these configuration complexities do not depend on the nuclear charge Z. Moreover, the Fisher-Shannon measure is shown to quadratically depend on the principal quantum number n. Finally, sharp upper bounds to the Fisher-Shannon measure and the shape complexity of a general hydrogenic orbital are given in terms of the quantum numbers.Comment: 22 pages, 7 figures, accepted i

ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours

Activation of the ERK1/2 pathway is involved in malignant transformation both in vitro and in vivo. Little is known about the role of activated ERK1/2 in non-small cell lung cancer (NSCLC). The purpose of this study was to characterise the extent of the activation of ERK1/2 by immunohistochemistry in patients with NSCLC, and to determine the relationship of ERK1/2 activation with clinicopathological variables. Specimens from 111 patients with NSCLC (stages I-IV) were stained for P-ERK. Staining for epidermal growth factor receptor (EGFR) and Ki-67 was also performed. In all, 34% of the tumour specimens showed activation for ERK1/2, while normal lung epithelial tissue was consistently negative. There was a strong statistical correlation between nuclear and cytoplasmic P-ERK staining and advanced stages (P<0.05 and P<0.001, respectively), metastatic hilar or mediastinal lymph nodes (P<0.01, P<0.001), and higher T stages (P<0.01, P<0.001). We did not find correlation of nuclear or cytoplasmic P-ERK staining with either EGFR expression or Ki-67 expression. Total ERK1/2 expression was evaluated with a specific ERK1/2 antibody and showed that P-ERK staining was not due to ERK overexpression but rather to hyperactivation of ERK1/2. Patients with a positive P-ERK cytoplasmic staining had a significant lower survival (P<0.05). However, multivariate analysis did not show significant survival difference. Our study indicates that nuclear and cytoplasmic ERK1/2 activation positively correlates with stage, T and lymph node metastases, and thus, is associated with advanced and aggressive NSCLC tumours