The Toxoplasma gondii plastid replication and repair enzyme complex, PREX

A plastid-like organelle, the apicoplast, is essential to the majority of medically and veterinary important apicomplexan protozoa including Toxoplasma gondii and Plasmodium. The apicoplast contains multiple copies of a 35 kb genome, the replication of which is dependent upon nuclear-encoded proteins that are imported into the organelle. In P. falciparum an unusual multi-functional gene, pfprex, was previously identified and inferred to encode a protein with DNA primase, DNA helicase and DNA polymerase activities. Herein, we report the presence of a prex orthologue in T. gondii. The protein is predicted to have a bi-partite apicoplast targeting sequence similar to that demonstrated on the PfPREX polypeptide, capable of delivering marker proteins to the apicoplast. Unlike the P. falciparum gene that is devoid of introns, the T. gondii prex gene carries 19 introns, which are spliced to produce a contiguous mRNA. Bacterial expression of the polymerase domain reveals the protein to be active. Consistent with the reported absence of a plastid in Cryptosporidium species, in silico analysis of their genomes failed to demonstrate an orthologue of prex. These studies indicate that prex is conserved across the plastid-bearing apicomplexans and may play an important role in the replication of the plastid genome

The Toxoplasma gondii Plastid replication and Repair Enzyme Complex, PREX

A plastid-like organelle, the apicoplast, is essential to the majority of medically and veterinary important apicomplexan protozoa including Toxoplasma gondii and Plasmodium. The apicoplast contains multiple copies of a 35 kb genome, the replication of which is dependent upon nuclear-encoded proteins that are imported into the organelle. In P. falciparum an unusual multi-functional gene, pfprex, was previously identified and inferred to encode a protein with DNA primase, DNA helicase and DNA polymerase activities. Herein, we report the presence of a prex orthologue in T. gondii. The protein is predicted to have a bi-partite apicoplast targeting sequence similar to that demonstrated on the PfPREX polypeptide, capable of delivering marker proteins to the apicoplast. Unlike the P. falciparum gene that is devoid of introns, the T. gondii prex gene carries 19 introns, which are spliced to produce a contiguous mRNA. Bacterial expression of the polymerase domain reveals the protein to be active. Consistent with the reported absence of a plastid in Cryptosporidium species, in silico analysis of their genomes failed to demonstrate an orthologue of prex. These studies indicate that prex is conserved across the plastid-bearing apicomplexans and may play an important role in the replication of the plastid genom

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis

Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. The role of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown. Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. miRNA expression was tracked over time post-hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c-5p was not detected in the plasma or within HDL, suggesting rHDL specifically targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu-miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in a time-dependent and site-specific manner. The early regulation of miRNAs, particularly miR-181c-5p, may underpin the rescue of diabetes-impaired angiogenesis by rHDL and has implications for the treatment of diabetes-related vascular complications

Frizzled-1 receptor regulates adult hippocampal neurogenesis

Indexación: Web of Science; Scopus.Background: In the adult hippocampus new neurons are continuously generated from neural stem cells (NSCs) present at the subgranular zone of the dentate gyrus. This process is controlled by Wnt signaling, which plays a complex role in regulating multiple steps of neurogenesis including maintenance, proliferation and differentiation of progenitor cells and the development of newborn neurons. Differential effects of Wnt signaling during progression of neurogenesis could be mediated by cell-type specific expression of Wnt receptors. Here we studied the potential role of Frizzled-1 (FZD1) receptor in adult hippocampal neurogenesis. Results: In the adult dentate gyrus, we determined that FZD1 is highly expressed in NSCs, neural progenitors and immature neurons. Accordingly, FZD1 is expressed in cultured adult hippocampal progenitors isolated from mouse brain. To evaluate the role of this receptor in vivo we targeted FZD1 in newborn cells using retroviral-mediated RNA interference. FZD1 knockdown resulted in a marked decrease in the differentiation of newborn cells into neurons and increased the generation of astrocytes, suggesting a regulatory role for the receptor in cell fate commitment. In addition, FZD1 knockdown induced an extended migration of adult-born neurons within the granule cell layer. However, no differences were observed in total dendritic length and dendritic arbor complexity between control and FZD1-deficient newborn neurons. Conclusions: Our results show that FZD1 regulates specific stages of adult hippocampal neurogenesis, being required for neuronal differentiation and positioning of newborn neurons into the granule cell layer, but not for morphological development of adult-born granule neurons.https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-016-0209-

Evidences of volcanic unrest on high-temperature fumaroles by satellite thermal monitoring: The case of Santa Ana volcano, El Salvador

International audienceOn October 1st, 2005, Santa Ana volcano (El Salvador) underwent a VEI 3 phreatomagmatic eruption after approximately one century of rest. Casualties and damages to some of the local infrastructures and surrounding plantations were followed by the evacuation of the nearby communities. The analysis of MODIS (Moderate Resolution Imaging Spectroradiometer) infrared data reveals that the main explosion was preceded by a one-year-long thermal unrest, associated to the development of a fumaroles field, located at the western rim of the summit crater lake. By combining space-based thermal flux and ground-based measurements (seismicity, sulfur emissions and lake temperatures), we suggest that the activity observed at Santa Ana between 2004 and 2005 was driven by the gradual intrusion of an undegassed magma body at a very shallow depth. Magma injection induced thermal anomalies associated with sustained degassing from the fumaroles field and promoted the interaction between the magmatic-hydrothermal system and the overlying water table. This process culminated into the VEI 3 phreatomagmatic eruption of October 2005 that strongly modified the shallow structure of the crater area. The subsequent three-years-long activity resulted from self-sealing of the fracture system and by the opening of a new fracture network directly connecting the deeper hydrothermal system with the crater lake. Our results show that satellite-based thermal data allow us to detect the expansion of the high-temperature fumarolic field. This may precede an explosive eruption and/or a lava dome extrusion. In particular, we show that thermal records can be analyzed with other geochemical (i.e. SO2 emissions) and geophysical (seismicity) data to track a shallow magmatic intrusion interacting with the surrounding hydrothermal system. This provides a remarkable support for volcano monitoring and eruption forecasting, particularly in remote areas where permanent ground data acquisition is hazardous, expensive and difficult

Deutsch-senegalesische Transferbeziehungen: Möglichkeiten einer interkulturellen Kommunikation anhand der deutschen Übersetzung von Mariama Bâs 'Une si longue lettre (Ein so langer Brief)'

Der Beitrag fokussiert auf die interkulturelle Kommunikation aus Sicht des deutsch-senegalesischen Kulturtransfers anhand von Literatur und Übersetzung. In dieser Hinsicht wird die Bedeutung der Übersetzer senegalesischer Literatur sowie deren Rezeption im deutschsprachigen Kontext herausgestellt. Der Dichterpräsident Léopold Sédar Senghor spielt dabei eine besondere Rolle sowohl hinsichtlich seiner Beschäftigung mit der deutschen Sprache, Kultur und Landeskunde als auch im Hinblick auf vorliegende deutsche Übersetzungen seines literarischen Schaffens. Hiervon ausgehend und gerade im Hinblick auf theoretische Ansätze zu interkulturellen Fragestellungen im Zusammenhang mit Übersetzung wird am Beispiel der deutschen Übersetzung von Mariama Bâs Roman 'Une si longue lettre' unter dem Titel 'Ein so langer Brief: ein afrikanisches Frauenschicksal' die Vermittlung kultureller Inhalte (im Hinblick auf Ort, Geschichte, Gesellschaft, Religion, Interaktion etc.) im deutsch-senegalesischen Kontext betrachtet.This contribution deals with intercultural communication in the frame of German-Senegalese cultural transfer through literature and translation. In this sense, I point out the importance of the translators of Senegalese literature as well as its reception in the German speaking area. The poet president Léopold Sédar Senghor played an important role in this context. He was much interested in German language, culture and civilization, and his literary works were translated into German as well. sing my analysis on theoretical approaches related to intercultural issues linked to translation, I examine the transmission of cultural information (in relation with place, history, society, religion, interaction etc.) in the translation of Mariama Bâ´s novel 'Une si longue lettre (Ein so langer Brief: ein afrikanisches Frauenschicksal) in the German-Senegalese context

Brazilian spring wheat germplasm as source of genetic variability.

As part of a Canada-Brazil germplasm exchange, 106 modern and ancient Brazilian spring wheat cultivars have been genotyped and phenotypically evaluated in Canada since 201

Learning to Control a Brain–Machine Interface for Reaching and Grasping by Primates

Reaching and grasping in primates depend on the coordination of neural activity in large frontoparietal ensembles. Here we demonstrate that primates can learn to reach and grasp virtual objects by controlling a robot arm through a closed-loop brain–machine interface (BMIc) that uses multiple mathematical models to extract several motor parameters (i.e., hand position, velocity, gripping force, and the EMGs of multiple arm muscles) from the electrical activity of frontoparietal neuronal ensembles. As single neurons typically contribute to the encoding of several motor parameters, we observed that high BMIc accuracy required recording from large neuronal ensembles. Continuous BMIc operation by monkeys led to significant improvements in both model predictions and behavioral performance. Using visual feedback, monkeys succeeded in producing robot reach-and-grasp movements even when their arms did not move. Learning to operate the BMIc was paralleled by functional reorganization in multiple cortical areas, suggesting that the dynamic properties of the BMIc were incorporated into motor and sensory cortical representations