Neural stem cells, inflammation and NF-kappaB: basic principle of maintenance and repair or origin of brain tumours?

Several recent reports suggest that inflammatory signals play a decisive role in the self-renewal, migration and differentiation of multipotent neural stem cells (NSCs). NSCs are believed to be able to ameliorate the symptoms of several brain pathologies through proliferation, migration into the area of the lesion and either differentiation into the appropriate cell type or secretion of anti-inflammatory cytokines. Although NSCs have beneficial roles, current evidence indicates that brain tumours, such as astrogliomas or ependymomas are also caused by tumour-initiating cells with stem-like properties. However, little is known about the cellular and molecular processes potentially generating tumours from NSCs. Most pro-inflammatory conditions are considered to activate the transcription factor NF-kappaB in various cell types. Strong inductive effects of NF-kappaB on proliferation and migration of NSCs have been described. Moreover, NF-kappaB is constitutively active in most tumour cells described so far. Chronic inflammation is also known to initiate cancer. Thus, NF-kappaB might provide a novel mechanistic link between chronic inflammation, stem cells and cancer. This review discusses the apparently ambivalent role of NF-kappaB: physiological maintenance and repair of the brain via NSCs, and a potential role in tumour initiation. Furthermore, it reveals a possible mechanism of brain tumour formation based on inflammation and NF-kappaB activity in NSCs.

Giving content to the principle of proportionality: happiness and pain as the universal currency for matching offence seriousness and penalty severity

The principle of proportionality prescribes that the punishment should equal the crime. It is one of the most important principles of sentencing. Yet, despite its widespread acceptance it offers no meaningful guide to sentencing. Hence penalty levels fluctuate greatly between jurisdictions and within jurisdictions. This is because there is no universally agreed criterion for measuring offence seriousness or penalty severity. This article suggests that the appropriate criteria for matching offence seriousness and penalty severity is the level of unhappiness or pain stemming from each of these impositions. Thus, for example, the level of pain meted out to a rape offender should equal the level of pain caused to a rape victim. Emerging scientific studies on human well-being and happiness show that human beings are similarly built in terms of the experiences that are either conducive or inimical to well-being. This commonality provides a strong foundation to be confident to make reasonably accurate predictions concerning the extent to which adverse events, such as being the victim of a criminal offence or subjected to a form of criminal sanction will stifle human flourishing. This will then allow us to match accurately offence seriousness and penalty level.

The common law principle of legality

In this age of statutes and human rights the common law principle of legality has assumed a central importance. The principle holds that '[u]nless the Parliament makes unmistakably clear its intention to abrogate or suspend a fundamental freedom, the courts will not construe a statute as having that operation.' This development has occurred throughout the common law world most relevantly in New Zealand and the United Kingdom where its re-emergence coincided with the enactment of statutory bill of rights. It is however the aim of this article to outline the nature and scope of the principle of legality in contemporary Australian law.

The principle of legality as clear statement rule: significance and problems

In Australia, the common law principle of legality has hardened into a strong clear statement rule that is applied when legislation engages common law rights and freedoms. It has transformed a loose collection of rebuttable interpretive presumptions into a quasi-constitutional common law bill of rights. However, these developments are not without controversy or issue. The analysis undertaken in this article suggests that the principle of legality as clear statement rule -- as mandated by the High Court in Coco v The Queen -- can only work legitimately if Parliament has clear and prior notice of the rights and freedoms that it operates to protect. But it is problematic if what a common law right, such as freedom of speech, requires or guarantees in any given legislative context is unclear and contested, and so must be judicially divined at the point of application. In these cases, the principle operates to enforce a (post-legislative) judicial approximation of what best protects and promotes an abstract legal value or principle. It amounts to the illegitimate judicial remaking of prior legislative decisions on rights. This undercuts the normative justifications for the principle of legality as it obscures from Parliament the common law (rights) backdrop against which its legislation is enacted and interpreted.

Determination of the LC50 of selamectin (active principle of the antiparasitic Revolution (R), Pfizer) applied on engorged female of the tick Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae)

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Testing the principle of equivalence by supernova neutrinos

We study the possible impact of the neutrino oscillation which could be induced by a tiny violation of equivalence principle (VEP) on the observation of neutrinos emitted from supernova driven by gravitational collapse. We show that using supernova neutrinos, one can probe very small values of VEP parameters, delta(tau) less than or similar to O(10(-31)) for massless or degenerated neutrinos and delta(tau) less than or similar to O(10(-16)) x (Deltam(2)/10(-5) eV(2)) for massive neutrinos. (C) 2002 Elsevier B.V. B.V. All rights reserved.

The δ expansion and the principle of minimal sensitivity

The δ-expansion is a nonperturbative approach for field theoretic models which combines the techniques of perturbation theory and the variational principle. Different ways of implementing the principle of minimal sensitivity to the δ-expansion produce in general different results for observables. For illustration we use the Nambu-Jona-Lasinio model for chiral symmetry restoration at finite density and compare results with those obtained with the Hartree-Fock approximation.

EMG activity of trunk stabilizer muscles during Centering Principle of Pilates Method

This study aimed to analyze the electromyographic (EMG) activity of iliocostalis lumborum (IL), internal oblique (IO) and multifidus (MU) and the antagonist cocontraction (IO/MU and IO/IL) during the performance of Centering Principle of Pilates Method. Participating in this study were eighteen young and physically fit volunteers, without experience in Pilates Method, divided in two groups: low back pain group (LBPG, n = 8) and control group (CG, n = 10). Two isometric contractions of IO muscles (Centering Principle) were performed in upright sitting posture. EMG signal amplitude was calculated by Root Mean Square (RMS), which was normalized by RMS maximum value. The common area method to calculate the antagonist cocontraction index was used. MU and IO activation and IO/MU cocontraction (. p < 0.05) were higher in CG. The CG therefore showed a higher stabilizer muscles recruitment than LBPG during the performance of Centering Principle of Pilates Method. © 2012 Elsevier Ltd.

Histopathology of the tegument of rabbits infested by Rhipicephalus sanguineus (ACARI: IXODIDAE) ticks and exposed to selamectin (active principle of acaricide Revolution®, Pfizer)

Ticks are hematophagous ectoparasites which can transmit several diseases to the host during their feeding process. When ticks mechanically damage the tissue, they eventually induce inflammatory responses on the skin spot where they are fixed. One of the alternatives to control these ectoparasites is the use of chemical substances like selamectin - the active principle of Pfizer's antiparasitic Revolution® - a macrocyclic lactone capable of doing neurotoxic damage to the tick and eventually eliminating infestation in dogs and cats. The purpose of this study was to analyze, using histological and histochemical techniques, the occurrence of morphophysiological alterations in the skin of the host rabbits exposed to selamectin and infested with Rhipicephalus sanguineus (Acari: Ixodidae). Histologically, the exposed and infested rabbits showed a partial and/or total decrease in the stratum corneum and the epithelium decreased in the number of cell layers, consequently reducing the stratification (thinning) and quite pronounced formations of sub-epidermal edemas with consequent disorganization of collagen fibers in the dermal layer's connective tissue. Histochemical tests showed strong periodic acid-Schiff-positive reaction in the hair follicle and some regions of the dermis, besides resynthesis of collagen fibers detected by Mallory's trichrome technique. The obtained results showed that selamectin acts like a toxicant agent when in contact with the skin of the rabbit infested with ticks, inducing morphophysiological alterations in the acute inflammatory process in the animal's tegument. Selamectin is a chemical substance which has a dose-dependent action since higher concentrations cause greater morphophysiological damage in the skin of rabbits. © 2013 Springer-Verlag Berlin Heidelberg.

Morphological alterations of epidermis of rabbits infested by R. sanguineus ticks and exposed to Selamectin (active principle of Pfizer Revolution (R) acaricide): A confocal microscopy study

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The Occurrence of Autophagic Cell Death in the Tegument of Rabbits Pre-Infested with Rhipicephalus sanguineus and Exposed to Selamectin (Active Principle of Acaricide Pfizer Revolution (R))

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