Targeting the NEDP1 enzyme to ameliorate ALS phenotypes through stress granule disassembly.

The elimination of aberrant inclusions is regarded as a therapeutic approach in neurodegeneration. In amyotrophic lateral sclerosis (ALS), mutations in proteins found within cytoplasmic condensates called stress granules (SGs) are linked to the formation of pathological SGs, aberrant protein inclusions, and neuronal toxicity. We found that inhibition of NEDP1, the enzyme that processes/deconjugates the ubiquitin-like molecule NEDD8, promotes the disassembly of physiological and pathological SGs.

Characterization of an Atypical eIF4E Ortholog in , LeishIF4E-6.

parasites are digenetic protists that shuffle between sand fly vectors and mammalian hosts, transforming from flagellated extracellular promastigotes that reside within the intestinal tract of female sand flies to the obligatory intracellular and non-motile amastigotes within mammalian macrophages. Stage differentiation is regulated mainly by post-transcriptional mechanisms, including translation regulation. parasites encode six different cap-binding proteins, LeishIF4E1-6, that show poor conservation with their counterparts from higher eukaryotes and among themselves.

LeishIF4E-5 Is a Promastigote-Specific Cap-Binding Protein in .

parasites cycle between sand fly vectors and mammalian hosts, transforming from extracellular promastigotes that reside in the vectors' alimentary canal to obligatory intracellular non-motile amastigotes that are harbored by macrophages of the mammalian hosts. The transition between vector and host exposes them to a broad range of environmental conditions that induces a developmental program of gene expression, with translation regulation playing a key role. The genome encodes six paralogs of the cap-binding protein eIF4E.

Stochastic Model for Energy Propagation in Disordered Granular Chains.

Energy transfer is one of the essentials of mechanical wave propagation (along with momentum transport). Here, it is studied in disordered one-dimensional model systems mimicking force-chains in real systems. The pre-stressed random masses (other types of disorder lead to qualitatively similar behavior) interact through (linearized) Hertzian repulsive forces, which allows solving the deterministic problem analytically.

A newly identified Leishmania IF4E-interacting protein, Leish4E-IP2, modulates the activity of cap-binding protein paralogs.

Translation of most cellular mRNAs in eukaryotes proceeds through a cap-dependent pathway, whereby the cap-binding complex, eIF4F, anchors the preinitiation complex at the 5' end of mRNAs and regulates translation initiation. The requirement of Leishmania to survive in changing environments can explain why they encode multiple eIF4E (LeishIF4Es) and eIF4G (LeishIF4Gs) paralogs, as each could be assigned a discrete role during their life cycle. Here we show that the expression and activity of different LeishIF4Es change during the growth of cultured promastigotes, urging a search for regulatory proteins.

LeishIF4E1 Deletion Affects the Promastigote Proteome, Morphology, and Infectivity.

parasites cycle between sand-fly vectors and mammalian hosts, adapting to changing environmental conditions by driving a stage-specific program of gene expression, which is tightly regulated by translation processes. encodes six eIF4E orthologs (LeishIF4Es) and five eIF4G candidates, forming different cap-binding complexes with potentially varying functions. Most LeishIF4E paralogs display temperature sensitivity in their cap-binding activity, except for LeishIF4E1, which maintains its cap-binding activity under all conditions.

Deletion of a Single LeishIF4E-3 Allele by the CRISPR-Cas9 System Alters Cell Morphology and Infectivity of .

The genomes of and trypanosomes encode six paralogs of the eIF4E cap-binding protein, known in other eukaryotes to anchor the translation initiation complex. In line with the heteroxenous nature of these parasites, the different LeishIF4E paralogs vary in their biophysical features and their biological behavior. We therefore hypothesize that each has a specialized function, not limited to protein synthesis.

Nutritional stress targets LeishIF4E-3 to storage granules that contain RNA and ribosome components in Leishmania.

Leishmania parasites lack pathways for de novo purine biosynthesis. The depletion of purines induces differentiation into virulent metacyclic forms. In vitro, the parasites can survive prolonged periods of purine withdrawal changing their morphology to long and slender cells with an extended flagellum, and decreasing their translation rates.

Rotational sound in disordered granular materials.

We numerically study the evolution of elastic standing waves in disordered disk systems with a focus on the dispersion relations of rotational sound. As on a lattice, the rotational mode exhibits an optical-like dispersion relation in the high frequency regime, representing a shoulder in the vibrational density of states and fast oscillations of the autocorrelations of rotational velocities. If tangential stiffness between the disks is large enough, a lattice-based model perfectly describes the dispersion relation of the rotational mode.

Testis mediated gene transfer: in vitro transfection in goat testis by electroporation.

Testis mediated gene transfer (TMGT) is a potential tool for making transgenic mice having more than 90% success rate. However, this method needs further standardization before it can be adapted in other species including livestock. In order to standardize the TMGT in goat, buck testes (n=20) collected from the slaughter house were injected with a vector driving green fluorescent protein (GFP) expression under a cytomegalovirus (CMV) promoter.