Regional and organ-level responses to local lung irradiation in sheep

Lung is a dose-limiting organ in radiotherapy. This may limit tumour control when effort is made in planning to limit the likelihood of radiation-induced lung injury (RILI). Understanding the factors that dictate susceptibility to radiation-induced pulmonary fibrosis will aid in the prevention and management of RILI, and may lead to more effective personalized radiotherapy treatment. As the interaction of regional and organ-level responses may shape the chronic consequences of RILI, we sought to characterise both aspects of the response in an ovine model. A defined volume of left pulmonary parenchyma was prescribed 5 fractions of 6 Gy within 14 days while the contralateral lung dose was constrained. Radiographic changes via computed tomography (CT) were documented to define differences in radio-exposed lung relative to non-exposed lung at d21, d63 and d171 (n = 2), and at d21, d147 and d227 (n = 2). Gross and histologic lung changes were evaluated in samples derived at necropsy examination to define the chronic pulmonary response to radiation. Irradiated lung demonstrated reduced radio-density and increased homogeneity as evidenced from texture based radiomic feature analysis, relative to the control lung. At necropsy, the radiation field was readily defined by pallor on the pleural surface, which was also evident on the cut surface of fixed lung specimens. The degree and homogeneity of pallor reflected the sparse presence of erythrocytes in alveolar septal capillaries of radiation-exposed lung. These changes contrasted with dilated and congested microvasculature in the contralateral control lung. Referencing data to measurements made in control lung volumes of sheep experiencing acute RILI indicated that interstitial collagen continues to deposit in the radio-exposed lung field. Overall lung vascularity increased during the chronic response, as evidenced by increased expression of endothelial cell marker (CD31); however, vascularity was consistently decreased in irradiated lung and was negatively correlated with lung collagen. Other organ-level responses included increased expression of alpha smooth muscle actin (ASMA), increased numbers of proliferating cells (Ki67 positive), and cells expressing the dendritic cell-lysosomal associated membrane protein (DC-LAMP) antigen. The chronic response to RILI in this model is effected at both the whole organ and local lung level. Whilst the long-term consequences of exposure to radiation involved the continued deposition of collagen in the radiation field, organ-level responses also included increased vascularization and increased expression of ASMA, Ki67 and DC-LAMP. Interrupting the interplay between these aspects may influence susceptibility to pulmonary fibrosis after radiotherapy. We advocate for the importance of large animal model systems in pursuing these opportunities to target local, organ-level and systemic mechanisms in parallel within the same subject over time

A Neuron-Glial Perspective for Computational Neuroscience

International audienceThere is growing excitement around glial cells, as compelling evidence point to new, previously unimaginable roles for these cells in information processing of the brain, with the potential to affect behavior and higher cognitive functions. Among their many possible functions, glial cells could be involved in practically every aspect of the brain physiology in health and disease. As a result, many investigators in the field welcome the notion of a Neuron-Glial paradigm of brain function, as opposed to Ramon y Cayal's more classical neuronal doctrine which identifies neurons as the prominent, if not the only, cells capable of a signaling role in the brain. The demonstration of a brain-wide Neuron-Glial paradigm however remains elusive and so does the notion of what neuron-glial interactions could be functionally relevant for the brain computational tasks. In this perspective, we present a selection of arguments inspired by available experimental and modeling studies with the aim to provide a biophysical and conceptual platform to computational neuroscience no longer as a mere prerogative of neuronal signaling but rather as the outcome of a complex interaction between neurons and glial cells

Shaping the European Union's security in the era of the fight against terrorism

Celem niniejszej pracy było przedstawienie procesu realizacji europejskiej „wojny z terroryzmem” oddziałującej na bezpieczeństwo Unii Europejskiej, zarówno z perspektywy pozytywnej, urzeczywistnionej przez instrumenty prawne, pozaprawne unijnej polityki antyterrorystycznej i wymierzonej wyłącznie wobec sprawców ataków terrorystycznych, jak i negatywnej, uderzającej bezpośrednio w obywateli Unii Europejskiej, osoby podejrzane o działalność terrorystyczną oraz w ich wartości (dobra), wynikające z racji bycia człowiekiem. W rozdziale pierwszym skoncentrowano się na wybranych aspektach terroryzmu – ewolucji pojęcia „terroryzm”; typologii zjawiska, ograniczając się do trzech kryterium: terytorialnego, podmiotowego i motywów działania terrorystów; charakterystyce organizacji terrorystycznych, które mają znaczny wpływ na poziom bezpieczeństwa państw europejskich (Al-Kaida, ETA, terroryści prawicowi) oraz metodach i środkach walki zamachowców. W rozdziale drugim opisano elementy polityki antyterrorystycznej UE – regulacje prawne i polityczne oraz ogólne i wyspecjalizowane agendy Unii w walce z terroryzmem – jako gwarancje bezpieczeństwa wewnętrznego Wspólnoty. Dla lepszego zobrazowania problemu w dalszej części uwzględniono efekty działania mechanizmów antyterrorystycznych Unii. W rozdziale trzecim jako w swoistym podsumowaniu pracy skupiono się na skutkach polityki antyterrorystycznej zaistniałych w państwach UE, z naciskiem na ograniczenie praw człowieka w imię zapewnienia bezpieczeństwa.The aim of this study was to present the implementation of a European "war on terror" that affects the security of the European Union both from the perspective of positive brought about by the legal instruments of the EU counter-terrorism policy extralegal and leveled only against the perpetrators of terrorist attacks as well as negative striking directly at European Union citizens, persons suspected of activities terrorist and their values (good) arising by virtue of being human. The first chapter focuses on selected aspects of terrorism - the evolution of the concept of "terrorism"; typology of the phenomenon limited to three criteria: government, subjective and motives of terrorists; characteristics of terrorist organizations which have a significant impact on the security of European countries (Al-Qaeda, ETA, right-wing terrorists) and the methods and means of combat bombers. The second chapter describes the elements of the EU counter-terrorism policy: legal regulations and political and general and specialized agencies of the Union in the fight against terrorism. To better illustrate the problem in the following into account the effects of the EU counter-terrorism mechanisms. The third chapter as a summary of the work focuses on the effects of anti-terrorist policy occurred in the EU with an emphasis on limiting human rights in the name of ensuring security

Identification of Physiological Substrates and Binding Partners of the Plant Mitochondrial Protease FTSH4 by the Trapping Approach

Maintenance of functional mitochondria is vital for optimal cell performance and survival. This is accomplished by distinct mechanisms, of which preservation of mitochondrial protein homeostasis fulfills a pivotal role. In plants, inner membrane-embedded i-AAA protease, FTSH4, contributes to the mitochondrial proteome surveillance. Owing to the limited knowledge of FTSH4’s in vivo substrates, very little is known about the pathways and mechanisms directly controlled by this protease. Here, we applied substrate trapping coupled with mass spectrometry-based peptide identification in order to extend the list of FTSH4’s physiological substrates and interaction partners. Our analyses revealed, among several putative targets of FTSH4, novel (mitochondrial pyruvate carrier 4 (MPC4) and Pam18-2) and known (Tim17-2) substrates of this protease. Furthermore, we demonstrate that FTSH4 degrades oxidatively damaged proteins in mitochondria. Our report provides new insights into the function of FTSH4 in the maintenance of plant mitochondrial proteome

1-Acetyl-17-{2-hydroxy-3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}-17-azapentacyclo[6.6.5.02,7.09,14.015,19]nonadeca-2,4,6,9,11,13-hexaene-16,18-dione

The title compound was synthesized by condensation of an oxiran imide derivative with an appropriate amine and its IR, 1H NMR, 13C NMR and mass spectroscopic data are reported. The synthesized compound was evaluated for its cytotoxicity and anti-HIV-1 activity in MT-4 cells