511 research outputs found
International Human Rights: Islam\u27s Friend or Foe? Algeria as an Example of the Compatibility of International Human Rights Regarding Women\u27s Equality and Islamic Law
Part I of this Note briefly discusses the development of International Human Rights Law as embodied in international covenants today. Part I also discusses Islamic law, the traditional role of women under Islamic law and culture, Algeria\u27s Constitution and Family Code, and other dynamics specific to Algeria that have hindered women\u27s obtainment of equal rights in the modern era. Part II presents the debate between conservative Islamists who argue that international principles of human rights law are incompatible with Islamic law and the scholars who assert that the two are compatible. Part III, by focusing on fundamental principles underlying the provisions in both the international human rights doctrine and Islamic law, argues that international human rights provisions granting women equal status with men comport with Islamic law principles as much as do legal documents that the Algerian Government has drafted. This Note concludes that the deprivation of women\u27s equal rights based on the claim of conflict with Islamic law is unjustified and that the example of Algeria proves that Islamic countries can and should protect human rights without regard to gender
Correction of the consequences of mitochondrial 3243A>G mutation in the MT-TL1 gene causing the MELAS syndrome by tRNA import into mitochondria
Mutations in human mitochondrial DNA are often associated with incurable human neuromuscular diseases. Among these mutations, an important number have been identified in tRNA genes, including 29 in the gene MT-TL1 coding for the tRNALeu(UUR). The m.3243A>G mutation was described as the major cause of the MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). This mutation was reported to reduce tRNALeu(UUR) aminoacylation and modification of its anti-codon wobble position, which results in a defective mitochondrial protein synthesis and reduced activities of respiratory chain complexes. In the present study, we have tested whether the mitochondrial targeting of recombinant tRNAs bearing the identity elements for human mitochondrial leucyl-tRNA synthetase can rescue the phenotype caused by MELAS mutation in human transmitochondrial cybrid cells. We demonstrate that nuclear expression and mitochondrial targeting of specifically designed transgenic tRNAs results in an improvement of mitochondrial translation, increased levels of mitochondrial DNA-encoded respiratory complexes subunits, and significant rescue of respiration. These findings prove the possibility to direct tRNAs with changed aminoacylation specificities into mitochondria, thus extending the potential therapeutic strategy of allotopic expression to address mitochondrial disorders
Mitochondrial Lysyl-tRNA Synthetase Independent Import of tRNA Lysine into Yeast Mitochondria
Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present for the import of lysyl tRNA in yeast
'Divided they stand, divided they fail': opposition politics in Morocco
The literature on democratization emphasises how authoritarian constraints usually lead genuine opposition parties and movements to form alliances in order to make demands for reform to the authoritarian regime. There is significant empirical evidence to support this theoretical point. While this trend is partly visible in the Middle East and North Africa, such coalitions are usually short-lived and limited to a single issue, never reaching the stage of formal and organic alliances. This article, using the case of Morocco, seeks to explain this puzzle by focusing on ideological and strategic differences that exist between the Islamist and the secular/liberal sectors of civil society, where significant opposition politics occurs. In addition, this article also aims to explain how pro-democracy strategies of the European Union further widen this divide, functioning as a key obstacle to democratic reforms
Method of carrier-free delivery of therapeutic RNA importable into human mitochondria: Lipophilic conjugates with cleavable bonds:
Defects in mitochondrial DNA often cause neuromuscular pathologies, for which no efficient therapy has yet been developed. MtDNA targeting nucleic acids might therefore be promising therapeutic candidates. Nevertheless, mitochondrial gene therapy has never been achieved because DNA molecules can not penetrate inside mitochondria in vivo. In contrast, some small non-coding RNAs are imported into mitochondrial matrix, and we recently designed mitochondrial RNA vectors that can be used to address therapeutic oligoribonucleotides into human mitochondria. Here we describe an approach of carrier-free targeting of the mitochondrially importable RNA into living human cells. For this purpose, we developed the protocol of chemical synthesis of oligoribonucleotides conjugated with cholesterol residue through cleavable covalent bonds. Conjugates containing pH-triggered hydrazone bond were stable during the cell transfection procedure and rapidly cleaved in acidic endosomal cellular compartments. RNAs conjugated to cholesterol through a hydrazone bond were characterized by efficient carrier-free cellular uptake and partial co-localization with mitochondrial network. Moreover, the imported oligoribonucleotide designed to target a pathogenic point mutation in mitochondrial DNA was able to induce a decrease in the proportion of mutant mitochondrial genomes. This newly developed approach can be useful for a carrier-free delivery of therapeutic RNA into mitochondria of living human cells
Induced tRNA import into human mitochondria: implication of a host aminoacyl-tRNA-synthetase:
In human cell, a subset of small non-coding RNAs is imported into mitochondria from the cytosol. Analysis of the tRNA import pathway allowing targeting of the yeast tRNA(Lys)(CUU) into human mitochondria demonstrates a similarity between the RNA import mechanisms in yeast and human cells. We show that the cytosolic precursor of human mitochondrial lysyl-tRNA synthetase (preKARS2) interacts with the yeast tRNA(Lys)(CUU) and small artificial RNAs which contain the structural elements determining the tRNA mitochondrial import, and facilitates their internalization by isolated human mitochondria. The tRNA import efficiency increased upon addition of the glycolytic enzyme enolase, previously found to be an actor of the yeast RNA import machinery. Finally, the role of preKARS2 in the RNA mitochondrial import has been directly demonstrated in vivo, in cultured human cells transfected with the yeast tRNA and artificial importable RNA molecules, in combination with preKARS2 overexpression or downregulation by RNA interference. These findings suggest that the requirement of protein factors for the RNA mitochondrial targeting might be a conserved feature of the RNA import pathway in different organisms
A mosaic of RNA binding and protein interaction motifs in a bifunctional mitochondrial tRNA import factor from Leishmania tropica
Proteins that participate in the import of cytosolic tRNAs into mitochondria have been identified in several eukaryotic species, but the details of their interactions with tRNA and other proteins are unknown. In the kinetoplastid protozoon Leishmania tropica, multiple proteins are organized into a functional import complex. RIC8A, a tRNA-binding subunit of this complex, has a C-terminal domain that functions as subunit 6b of ubiquinol cytochrome c reductase (complex III). We show that the N-terminal domain, unique to kinetoplastid protozoa, is structurally similar to the appended S15/NS1 RNA-binding domain of aminoacyl tRNA synthetases, with a helixâturnâhelix motif. Structure-guided mutagenesis coupled with in vitro assays showed that helix α1 contacts tRNA whereas helix α2 targets the protein for assembly into the import complex. Inducible expression of a helix 1-deleted variant in L. tropica resulted in formation of an inactive import complex, while the helix 2-deleted variant was unable to assemble in vivo. Moreover, a protein-interaction assay showed that the C-terminal domain makes allosteric contacts with import receptor RIC1 complexed with tRNA. These results help explain the origin of the bifunctionality of RIC8A, and the allosteric changes accompanying docking and release of tRNA during import
Self-Consistent Model of Annihilation-Diffusion Reaction with Long-Range Interactions
We introduce coarse-grained hydrodynamic equations of motion for
diffusion-annihilation system with a power-law long-range interaction. By
taking into account fluctuations of the conserved order parameter - charge
density - we derive an analytically solvable approximation for the nonconserved
order parameter - total particle density. Asymptotic solutions are obtained for
the case of random Gaussian initial conditions and for system dimensionality . Large-t, intermediate-t and small-t asymptotics were calculated and
compared with existing scaling theories, exact results and simulation data.Comment: 22 pages, RevTEX, 1 PostScript figur
Biological significance of 5S rRNA import into human mitochondria: role of ribosomal protein MRP-L18:
5S rRNA is an essential component of ribosomes of all living organisms, the only known exceptions being mitochondrial ribosomes of fungi, animals, and some protists. An intriguing situation distinguishes mammalian cells: Although the mitochondrial genome contains no 5S rRNA genes, abundant import of the nuclear DNA-encoded 5S rRNA into mitochondria was reported. Neither the detailed mechanism of this pathway nor its rationale was clarified to date. In this study, we describe an elegant molecular conveyor composed of a previously identified human 5S rRNA import factor, rhodanese, and mitochondrial ribosomal protein L18, thanks to which 5S rRNA molecules can be specifically withdrawn from the cytosolic pool and redirected to mitochondria, bypassing the classic nucleolar reimport pathway. Inside mitochondria, the cytosolic 5S rRNA is shown to be associated with mitochondrial ribosomes
Landau level mixing and spin degeneracy in the quantum Hall effect
We study dynamics of electrons in a magnetic field using a network model with
two channels per link with random mixing in a random intrachannel potential;
the channels represent either two Landau levels or two spin states. We consider
channel mixing as function of the energy separation of the two extended states
and show that its effect changes from repulsion to attraction as the energy
separation increases. For two Landau levels this leads to level floating at low
magnetic fields while for Zeeman split spin states we predict level attraction
at high magnetic fields, accounting for ESR data. We also study random mixing
of two degenerate channels, while the intrachannel potential is periodic
(non-random). We find a single extended state with a localization exponent
for real scattering at nodes; the general case has also a
single extended state, though the localized nature of nearby states sets in at
unusually large scales.Comment: 18 pages, 11 tex-files and 1 ps-file of figure
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