193 research outputs found
Drafting Tunisiaβs constitution : tensions between constituent power and constituted power in the transition process
After a series of votes on each of the 149 articles of the constitution, the Tunisian National Constituent Assembly (ANC) adopted a new constitution on 26 January 2014 which was signed into law by President Mouncef Marzouki the following day. It marked the end of a period of political tension that rocked the country since the summer of 2013, when on 1 June the assembly, dominated by the Islamist Ennahda Movement, presented an Islamo-conservative constitution. This proposal was followed by the assassination of the ANC member and opposition politician Mohamed Brahmi on 26 July and Egyptβs military coup on 3 July 2013. This paper will analyse the tensions surrounding the two and a half year constitution-making process from the two core legal concepts of constituent power and constituted power. Drawing on the theoretical work of Thornhill, I will argue that key to the success of Tunisia in tempering tensions was the role of the judiciary in pre-revolutionary Tunisia as well as the appearance of other extra-judicial actors in the constitution-making process. This was complemented by significant references to international law and rights. During the process of drafting the constitution, the judiciary refrained from attempting to establish its autonomy or supremacy in deciding the correct application of law. Due to this, the elected assembly was charged with the unique task of establishing a legal-rational framework without the constraints imposed by common laws or an autonomous and semi-emancipated judiciary. While it is not possible to assert that this unique situation made the transition to institutionalised liberal-democratic rule possible, this paper will argue that Tunisiaβs relative stability was at the very least facilitated by the fact that the judiciary remained in the background, denying antagonistic actors access to this institution in order to express their opposition to developing constitutional rule and practice
Human rights in Moroccan politics
In the early 1990s, the question of human rights was one of the central issues where the Kingdom of Morocco encountered domestic and international criticism. As a consequence, Morocco embarked on a political reform programme in order to improve its image abroad and in order to create a domestic consensus among political forces. This had positive effects on political liberties that Moroccans enjoyed but its character remained limited through the absence of independent institutions of checks and balances.peer-reviewe
Correlated changes between regulatory cis elements and condition-specific expression in paralogous gene families
Gene duplication is integral to evolution, providing novel opportunities for organisms to diversify in function. One fundamental pathway of functional diversification among initially redundant gene copies, or paralogs, is via alterations in their expression patterns. Although the mechanisms underlying expression divergence are not completely understood, transcription factor binding sites and nucleosome occupancy are known to play a significant role in the process. Previous attempts to detect genomic variations mediating expression divergence in orthologs have had limited success for two primary reasons. First, it is inherently challenging to compare expressions among orthologs due to variable trans-acting effects and second, previous studies have quantified expression divergence in terms of an overall similarity of expression profiles across multiple samples, thereby obscuring condition-specific expression changes. Moreover, the inherently inter-correlated expressions among homologs present statistical challenges, not adequately addressed in many previous studies. Using rigorous statistical tests, here we characterize the relationship between cis element divergence and condition-specific expression divergence among paralogous genes in Saccharomyces cerevisiae. In particular, among all combinations of gene family and TFs analyzed, we found a significant correlation between TF binding and the condition-specific expression patterns in over 20% of the cases. In addition, incorporating nucleosome occupancy reveals several additional correlations. For instance, our results suggest that GAL4 binding plays a major role in the expression divergence of the genes in the sugar transporter family. Our work presents a novel means of investigating the cis regulatory changes potentially mediating expression divergence in paralogous gene families under specific conditions
Increased ion temperature and neutron yield observed in magnetized indirectly driven D_{2}-filled capsule implosions on the national ignition facility
The application of an external 26Β Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45Β MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be βΌ4.9ββkT using the 14.1Β MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30Β kV pulsed-power system to deliver a βΌ3ββΞΌs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment
TLR2 and Nod2 Mediate Resistance or Susceptibility to Fatal Intracellular Ehrlichia Infection in Murine Models of Ehrlichiosis
Our murine models of human monocytic ehrlichiosis (HME) have shown that severe and fatal ehrlichiosis is due to generation of pathogenic T cell responses causing immunopathology and multi-organ failure. However, the early events in the liver, the main site of infection, are not well understood. In this study, we examined the liver transcriptome during the course of lethal and nonlethal infections caused by Ixodes ovatus Ehrlichia and Ehrlichia muris, respectively. On day 3 post-infection (p.i.), although most host genes were down regulated in the two groups of infected mice compared to naΓ―ve counterparts, lethal infection induced significantly higher expression of caspase 1, caspase 4, nucleotide binding oligomerization domain-containing proteins (Nod1), tumor necrosis factor-alpha, interleukin 10, and CCL7 compared to nonlethal infection. On day 7 p.i., lethal infection induced highly significant upregulation of type-1 interferon, several inflammatory cytokines and chemokines, which was associated with increased expression levels of Toll-like receptor-2 (TLR2), Nod2, MyD88, nuclear factor-kappa B (NF-kB), Caspase 4, NLRP1, NLRP12, Pycard, and IL-1Ξ², suggesting enhanced TLR signals and inflammasomes activation. We next evaluated the participation of TLR2 and Nod2 in the host response during lethal Ehrlichia infection. Although lack of TLR2 impaired bacterial elimination and increased tissue necrosis, Nod2 deficiency attenuated pathology and enhanced bacterial clearance, which correlated with increased interferon-Ξ³ and interleukin-10 levels and a decreased frequency of pathogenic CD8+ T cells in response to lethal infection. Thus, these data indicate that Nod2, but not TLR2, contributes to susceptibility to severe Ehrlichia-induced shock. Together, our studies provide, for the first time, insight into the diversity of host factors and novel molecular pathogenic mechanisms that may contribute to severe HME. Β© 2013 Chattoraj et al
ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π°ΡΠ°Ρ ΠΈΡΠΎΠ²ΠΎΠ³ΠΎ ΠΌΠ°ΡΠ»Π° Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΡΠΈΡΠ°Π΄ΠΊΠΈ ΠΊ Π΄ΠΈΠ·Π΅Π»ΡΠ½ΠΎΠΌΡ ΡΠΎΠΏΠ»ΠΈΠ²Ρ
Abstract. As part of the environmental requirements for reducing the toxicity of exhaust gases of internal combustion engines, including diesel engines of tractor and combine harvesters, great attention is paid to various ways of reducing harmful substances in the exhaust gases combustion products. The problem of using energy-saving resources, including renewable energy, various types of alternative fuels is currently solved. In several ways these include using vegetable oils from various agricultural crops, one of which is peanut oil. Its use can help to solve two urgent problems: reducing the toxicity of exhaust gases of internal combustion engines. (Research objective) To analyze the properties of peanut oil as an additive to diesel fuel and evaluate the performance of a diesel engine using this type of fuel. (Materials and methods) The properties of peanut oil differ from those of diesel fuel by higher viscosity and lower heat value. To compensate for these shortcomings, kerosene has been added to the mixture of diesel fuel with peanut oil. In cold climatic conditions, the use of pure peanut oil is difficult, since its cloud point is 3.3 degrees Celsius, which is 20 degrees higher than that of diesel fuel. In the blend composition, the cloud point of the fuel decreases, which makes it possible to use it in colder conditions. (Results and discussion) The authors have conducted a study on the tractor engine D-120 coupled with a brake balancer installation without additional engine adjustments. As a result, they have obtained the characteristics of the engine working on fuel with the addition of peanut oil. The authors have compared the results of the engine operation on pure and mixed diesel fuel, revealed indicators of operating efficiency and toxicity of exhaust gases. (Conclusions) It has been proved experimentally that the addition of peanut oil to diesel fuel leads to a decrease in the specific effective fuel consumption, and also reduces the emission of soot and nitrogen oxides, while the engine power decreases slightly.Π Π΅ΡΠ΅ΡΠ°Ρ. Π ΡΠ°ΠΌΠΊΠ°Ρ
ΡΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΠ΅Π±ΠΎΠ²Π°Π½ΠΈΠΉ ΠΊ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ ΠΎΡΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΡ
Π³Π°Π·ΠΎΠ² Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»Π΅ΠΉ Π²Π½ΡΡΡΠ΅Π½Π½Π΅Π³ΠΎ ΡΠ³ΠΎΡΠ°Π½ΠΈΡ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ ΡΡΠ°ΠΊΡΠΎΡΠ½ΡΡ
ΠΈ ΠΊΠΎΠΌΠ±Π°ΠΉΠ½ΠΎΠ²ΡΡ
Π΄ΠΈΠ·Π΅Π»Π΅ΠΉ, Π±ΠΎΠ»ΡΡΠΎΠ΅ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ ΡΠ΄Π΅Π»ΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌ ΡΠΏΠΎΡΠΎΠ±Π°ΠΌ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ Π²ΡΠ΅Π΄Π½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ² Π² ΠΏΡΠΎΠ΄ΡΠΊΡΠ°Ρ
ΡΠ³ΠΎΡΠ°Π½ΠΈΡ ΡΠΎΠΏΠ»ΠΈΠ²Π°. Π Π΅ΡΠ°Π΅ΡΡΡ Π·Π°Π΄Π°ΡΠ° ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΡΠ½Π΅ΡΠ³ΠΎΡΠ±Π΅ΡΠ΅Π³Π°ΡΡΠΈΡ
ΡΠ΅ΡΡΡΡΠΎΠ², Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Π²ΠΎΠ·ΠΎΠ±Π½ΠΎΠ²Π»ΡΠ΅ΠΌΡΡ
ΠΈΡΡΠΎΡΠ½ΠΈΠΊΠΎΠ² ΡΠ½Π΅ΡΠ³ΠΈΠΈ, ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π°Π»ΡΡΠ΅ΡΠ½Π°ΡΠΈΠ²Π½ΡΡ
Π²ΠΈΠ΄ΠΎΠ² ΡΠΎΠΏΠ»ΠΈΠ²Π°. Π Π½ΠΈΠΌ ΠΎΡΠ½ΠΎΡΡΡΡΡ ΡΠ°ΡΡΠΈΡΠ΅Π»ΡΠ½ΡΠ΅ ΠΌΠ°ΡΠ»Π° ΡΠ΅Π»ΡΡΠΊΠΎΡ
ΠΎΠ·ΡΠΉΡΡΠ²Π΅Π½Π½ΡΡ
ΠΊΡΠ»ΡΡΡΡ, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Π°ΡΠ°Ρ
ΠΈΡΠΎΠ²ΠΎΠ΅. (Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ) ΠΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°ΡΡ ΡΠ²ΠΎΠΉΡΡΠ²Π° Π°ΡΠ°Ρ
ΠΈΡΠΎΠ²ΠΎΠ³ΠΎ ΠΌΠ°ΡΠ»Π° ΠΊΠ°ΠΊ Π΄ΠΎΠ±Π°Π²ΠΊΠΈ ΠΊ Π΄ΠΈΠ·Π΅Π»ΡΠ½ΠΎΠΌΡ ΡΠΎΠΏΠ»ΠΈΠ²Ρ ΠΈ ΠΎΡΠ΅Π½ΠΈΡΡ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ ΡΠ°Π±ΠΎΡΡ Π΄ΠΈΠ·Π΅Π»Ρ Π½Π° ΡΠΎΠΏΠ»ΠΈΠ²Π΅ Ρ Π΄ΠΎΠ±Π°Π²ΠΊΠ°ΠΌΠΈ Π°ΡΠ°Ρ
ΠΈΡΠΎΠ²ΠΎΠ³ΠΎ ΠΌΠ°ΡΠ»Π°. (ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ) ΠΡΠ°Ρ
ΠΈΡΠΎΠ²ΠΎΠ΅ ΠΌΠ°ΡΠ»ΠΎ ΠΎΡΠ»ΠΈΡΠ°Π΅ΡΡΡ ΠΎΡ Π΄ΠΈΠ·Π΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠΏΠ»ΠΈΠ²Π° Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠΎΠΊΠΎΠΉ Π²ΡΠ·ΠΊΠΎΡΡΡΡ ΠΈ ΠΌΠ΅Π½ΡΡΠ΅ΠΉ ΡΠ΅ΠΏΠ»ΠΎΡΠΎΠΉ ΡΠ³ΠΎΡΠ°Π½ΠΈΡ. Π ΡΠΌΠ΅ΡΡ Π΄ΠΈΠ·Π΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠΏΠ»ΠΈΠ²Π° Ρ Π°ΡΠ°Ρ
ΠΈΡΠΎΠ²ΡΠΌ ΠΌΠ°ΡΠ»ΠΎΠΌ Π΄ΠΎΠ±Π°Π²Π»ΡΠ»ΠΈ ΠΊΠ΅ΡΠΎΡΠΈΠ½ Π΄Π»Ρ ΠΊΠΎΠΌΠΏΠ΅Π½ΡΠ°ΡΠΈΠΈ ΡΡΠΈΡ
Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠΎΠ². Π Ρ
ΠΎΠ»ΠΎΠ΄Π½ΡΡ
ΠΊΠ»ΠΈΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π°ΡΠ°Ρ
ΠΈΡΠΎΠ²ΠΎΠ³ΠΎ ΠΌΠ°ΡΠ»Π° Π² ΡΠΈΡΡΠΎΠΌ Π²ΠΈΠ΄Π΅ Π·Π°ΡΡΡΠ΄Π½Π΅Π½ΠΎ, ΡΠ°ΠΊ ΠΊΠ°ΠΊ Π΄Π»Ρ Π½Π΅Π³ΠΎ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ° ΠΏΠΎΠΌΡΡΠ½Π΅Π½ΠΈΡ ΡΠΎΡΡΠ°Π²Π»ΡΠ΅Ρ 3,3 Π³ΡΠ°Π΄ΡΡΠ° Π¦Π΅Π»ΡΡΠΈΡ, ΡΡΠΎ Π½Π° 20 Π³ΡΠ°Π΄ΡΡΠΎΠ² Π²ΡΡΠ΅, ΡΠ΅ΠΌ Ρ Π΄ΠΈΠ·Π΅Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠΏΠ»ΠΈΠ²Π°. Π ΡΠΌΠ΅ΡΠ΅Π²ΠΎΠΌ ΡΠΎΡΡΠ°Π²Π΅ ΡΠ΅ΠΌΠΏΠ΅ΡΠ°ΡΡΡΠ° ΠΏΠΎΠΌΡΡΠ½Π΅Π½ΠΈΡ ΡΠΎΠΏΠ»ΠΈΠ²Π° ΠΏΠΎΠ½ΠΈΠΆΠ°Π΅ΡΡΡ, ΡΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡ Π΅Π³ΠΎ Π² Π±ΠΎΠ»Π΅Π΅ Ρ
ΠΎΠ»ΠΎΠ΄Π½ΡΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
. (Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈ ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅) ΠΡΠΎΠ²Π΅Π»ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π½Π° ΡΡΠ°ΠΊΡΠΎΡΠ½ΠΎΠΌ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»Π΅ Π-120 Π² ΠΏΠ°ΡΠ΅ Ρ ΡΠΎΡΠΌΠΎΠ·Π½ΠΎΠΉ Π±Π°Π»Π°Π½ΡΠΈΡΠ½ΠΎΠΉ ΡΡΡΠ°Π½ΠΎΠ²ΠΊΠΎΠΉ Π±Π΅Π· Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ
ΡΠ΅Π³ΡΠ»ΠΈΡΠΎΠ²ΠΎΠΊ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»Ρ. ΠΠΎΠ»ΡΡΠΈΠ»ΠΈ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»Ρ ΠΏΡΠΈ ΡΠ°Π±ΠΎΡΠ΅ Π½Π° ΡΠΎΠΏΠ»ΠΈΠ²Π΅ Ρ Π΄ΠΎΠ±Π°Π²ΠΊΠΎΠΉ Π°ΡΠ°Ρ
ΠΈΡΠΎΠ²ΠΎΠ³ΠΎ ΠΌΠ°ΡΠ»Π°. Π‘ΡΠ°Π²Π½ΠΈΠ»ΠΈ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΠ°Π±ΠΎΡΡ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»Ρ Π½Π° ΡΠΈΡΡΠΎΠΌ Π΄ΠΈΠ·Π΅Π»ΡΠ½ΠΎΠΌ ΡΠΎΠΏΠ»ΠΈΠ²Π΅ ΠΈ ΡΠΌΠ΅ΡΠ΅Π²ΠΎΠΌ, Π²ΡΡΠ²ΠΈΠ»ΠΈ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠ°Π±ΠΎΡΡ ΠΈ ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ ΠΎΡΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΡ
Π³Π°Π·ΠΎΠ². (ΠΡΠ²ΠΎΠ΄Ρ) ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎ Π΄ΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ Π΄ΠΎΠ±Π°Π²ΠΊΠ° Π°ΡΠ°Ρ
ΠΈΡΠΎΠ²ΠΎΠ³ΠΎ ΠΌΠ°ΡΠ»Π° ΠΊ Π΄ΠΈΠ·Π΅Π»ΡΠ½ΠΎΠΌΡ ΡΠΎΠΏΠ»ΠΈΠ²Ρ ΡΠΎΠΊΡΠ°ΡΠ°Π΅Ρ ΡΠ΄Π΅Π»ΡΠ½ΡΠΉ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΉ ΡΠ°ΡΡ
ΠΎΠ΄ ΡΠΎΠΏΠ»ΠΈΠ²Π°, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΠΌΠ΅Π½ΡΡΠ°Π΅Ρ Π²ΡΠ±ΡΠΎΡ ΡΠ°ΠΆΠΈ ΠΈ ΠΎΠΊΡΠΈΠ΄ΠΎΠ² Π°Π·ΠΎΡΠ°, ΠΏΡΠΈ ΡΡΠΎΠΌ ΠΌΠΎΡΠ½ΠΎΡΡΡ Π΄Π²ΠΈΠ³Π°ΡΠ΅Π»Ρ ΡΠ½ΠΈΠΆΠ°Π΅ΡΡΡ Π½Π΅Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ
eXtraembryonic ENdoderm (XEN) Stem Cells Produce Factors that Activate Heart Formation
Initial specification of cardiomyocytes in the mouse results from interactions between the extraembryonic anterior visceral endoderm (AVE) and the nascent mesoderm. However the mechanism by which AVE activates cardiogenesis is not well understood, and the identity of specific cardiogenic factors in the endoderm remains elusive. Most mammalian studies of the cardiogenic potential of the endoderm have relied on the use of cell lines that are similar to the heart-inducing AVE. These include the embryonal-carcinoma-derived cell lines, END2 and PYS2. The recent development of protocols to isolate eXtraembryonic ENdoderm (XEN) stem cells, representing the extraembryonic endoderm lineage, from blastocyst stage mouse embryos offers new tools for the genetic dissection of cardiogenesis.Here, we demonstrate that XEN cell-conditioned media (CM) enhances cardiogenesis during Embryoid Body (EB) differentiation of mouse embryonic stem (ES) cells in a manner comparable to PYS2-CM and END2-CM. Addition of CM from each of these three cell lines enhanced the percentage of EBs that formed beating areas, but ultimately, only XEN-CM and PYS2-CM increased the total number of cardiomyocytes that formed. Furthermore, our observations revealed that both contact-independent and contact-dependent factors are required to mediate the full cardiogenic potential of the endoderm. Finally, we used gene array comparison to identify factors in these cell lines that could mediate their cardiogenic potential.These studies represent the first step in the use of XEN cells as a molecular genetic tool to study cardiomyocyte differentiation. Not only are XEN cells functionally similar to the heart-inducing AVE, but also can be used for the genetic dissection of the cardiogenic potential of AVE, since they can be isolated from both wild type and mutant blastocysts. These studies further demonstrate the importance of both contact-dependent and contact-independent factors in cardiogenesis and identify potential heart-inducing proteins in the endoderm
Activation of an NLRP3 Inflammasome Restricts Mycobacterium kansasii Infection
Mycobacterium kansasii has emerged as an important nontuberculous mycobacterium pathogen, whose incidence and prevalence have been increasing in the last decade. M. kansasii can cause pulmonary tuberculosis clinically and radiographically indistinguishable from that caused by Mycobacterium tuberculosis infection. Unlike the widely-studied M. tuberculosis, little is known about the innate immune response against M. kansasii infection. Although inflammasome activation plays an important role in host defense against bacterial infection, its role against atypical mycobacteria remains poorly understood. In this report, the role of inflammasome activity in THP-1 macrophages against M. kansasii infection was studied. Results indicated that viable, but not heat-killed, M. kansasii induced caspase-1-dependent IL-1Ξ² secretion in macrophages. The underlying mechanism was found to be through activation of an inflammasome containing the NLR (Nod-like receptor) family member NLRP3 and the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). Further, potassium efflux, lysosomal acidification, ROS production and cathepsin B release played a role in M. kansasii-induced inflammasome activation. Finally, the secreted IL-1Ξ² derived from caspase-1 activation was shown to restrict intracellular M. kansasii. These findings demonstrate a biological role for the NLRP3 inflammasome in host defense against M. kansasii
A Comparative Analysis of Extra-Embryonic Endoderm Cell Lines
Prior to gastrulation in the mouse, all endodermal cells arise from the primitive
endoderm of the blastocyst stage embryo. Primitive endoderm and its derivatives
are generally referred to as extra-embryonic endoderm (ExEn) because the
majority of these cells contribute to extra-embryonic lineages encompassing the
visceral endoderm (VE) and the parietal endoderm (PE). During gastrulation, the
definitive endoderm (DE) forms by ingression of cells from the epiblast. The DE
comprises most of the cells of the gut and its accessory organs. Despite their
different origins and fates, there is a surprising amount of overlap in marker
expression between the ExEn and DE, making it difficult to distinguish between
these cell types by marker analysis. This is significant for two main reasons.
First, because endodermal organs, such as the liver and pancreas, play important
physiological roles in adult animals, much experimental effort has been directed
in recent years toward the establishment of protocols for the efficient
derivation of endodermal cell types in vitro. Conversely,
factors secreted by the VE play pivotal roles that cannot be attributed to the
DE in early axis formation, heart formation and the patterning of the anterior
nervous system. Thus, efforts in both of these areas have been hampered by a
lack of markers that clearly distinguish between ExEn and DE. To further
understand the ExEn we have undertaken a comparative analysis of three ExEn-like
cell lines (END2, PYS2 and XEN). PYS2 cells are derived from embryonal
carcinomas (EC) of 129 strain mice and have been characterized as parietal
endoderm-like [1], END2 cells are derived from P19 ECs and
described as visceral endoderm-like, while XEN cells are derived from blastocyst
stage embryos and are described as primitive endoderm-like. Our analysis
suggests that none of these cell lines represent a bona fide
single in vivo lineage. Both PYS2 and XEN cells represent mixed
populations expressing markers for several ExEn lineages. Conversely END2 cells,
which were previously characterized as VE-like, fail to express many markers
that are widely expressed in the VE, but instead express markers for only a
subset of the VE, the anterior visceral endoderm. In addition END2 cells also
express markers for the PE. We extended these observations with microarray
analysis which was used to probe and refine previously published data sets of
genes proposed to distinguish between DE and VE. Finally, genome-wide pathway
analysis revealed that SMAD-independent TGFbeta signaling through a TAK1/p38/JNK
or TAK1/NLK pathway may represent one mode of intracellular signaling shared by
all three of these lines, and suggests that factors downstream of these pathways
may mediate some functions of the ExEn. These studies represent the first step
in the development of XEN cells as a powerful molecular genetic tool to study
the endodermal signals that mediate the important developmental functions of the
extra-embryonic endoderm. Our data refine our current knowledge of markers that
distinguish various subtypes of endoderm. In addition, pathway analysis suggests
that the ExEn may mediate some of its functions through a non-classical MAP
Kinase signaling pathway downstream of TAK1
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