LeishIF4E2 is a cap-binding protein that plays a role in Leishmania cell cycle progression.

Leishmania encode six paralogs of the cap-binding protein eIF4E and five eIF4G candidates, forming unique complexes. Two cap-binding proteins, LeishIF4E1 and LeishIF4E2, do not bind any identified LeishIF4Gs, thus their roles are intriguing. Here, we combine structural prediction, proteomic analysis, and interaction assays to shed light on LeishIF4E2 function.

LeishIF3d is a non-canonical cap-binding protein in .

Translation of most cellular mRNAs in eukaryotes proceeds through a cap-dependent pathway, whereby the cap-binding complex, eIF4F, anchors the pre-initiation complex at the 5' end of mRNAs driving translation initiation. The genome of encodes a large repertoire of cap-binding complexes that fulfill a variety of functions possibly involved in survival along the life cycle. However, most of these complexes function in the promastigote life form that resides in the sand fly vector and decrease their activity in amastigotes, the mammalian life form.

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.

Distinct features of the Leishmania cap-binding protein LeishIF4E2 revealed by CRISPR-Cas9 mediated hemizygous deletion.

Leishmania parasites cycle between sand-fly vectors and mammalian hosts adapting to alternating environments by stage-differentiation accompanied by changes in the proteome profiles. Translation regulation plays a central role in driving the differential program of gene expression since control of gene regulation in Leishmania is mostly post-transcriptional. The Leishmania genome encodes six eIF4E paralogs, some of which bind a dedicated eIF4G candidate, and each eIF4E is assumed to have specific functions with perhaps some overlaps.

A case for a "middle-way career" in the history of psychology: The work of pioneering psychoanalyst Marjorie Brierley in early 20th century Britain.

Historians often focus on the most famous or radical, prolific theoreticians among psychoanalysts, thereby at times reproducing the self-centered biases of their subjects rather than providing a useful critique. I offer instead a revisionist view of this history of psychology, arguing that we should pay more attention to a variety of middle-way actors who combined diverse forms of often-dismissed labor that included practice, editorial, and administrative work, and who tried to find a less rigid theoretical middle ground to toil. These middle-way actors were often women and although scholars have commented on the prominence of women in the early societies of psychoanalysis, we have not conducted adequate research on all these early active members and their roles.

ZnJ6 Is a Thylakoid Membrane DnaJ-Like Chaperone with Oxidizing Activity in .

Assembly of photosynthetic complexes is sensitive to changing light intensities, drought and pathogens, each of which induces a redox imbalance that requires the assistance of specific chaperones to maintain protein structure. Here we report a thylakoid membrane-associated DnaJ-like protein, ZnJ6 (Cre06.g251716.

New books on the early history of British psychoanalysis: An essay review.

Reviews the books, by John Forrester and Laura Cameron and by Philip Kuhn. Sigmund Freud and his invention of the discipline of psychoanalysis had an immense intellectual impact on 20th-century culture. Yet, although his writings were received with great enthusiasm-as well as with hostility-we are still lacking full accounts of all the various sites where Freud and his ideas were widely discussed and which rapidly paired his name (as early as the 1920s) with those of eminent intellectuals such as Karl Marx, Charles Darwin, and Albert Einstein.

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.

Structural basis for LeishIF4E-1 modulation by an interacting protein in the human parasite Leishmania major.

Leishmania parasites are unicellular pathogens that are transmitted to humans through the bite of infected sandflies. Most of the regulation of their gene expression occurs post-transcriptionally, and the different patterns of gene expression required throughout the parasites' life cycle are regulated at the level of translation. Here, we report the X-ray crystal structure of the Leishmania cap-binding isoform 1, LeishIF4E-1, bound to a protein fragment of previously unknown function, Leish4E-IP1, that binds tightly to LeishIF4E-1.

ZnJ2 Is a Member of a Large Chaperone Family in the Chloroplast of Photosynthetic Organisms that Features a DnaJ-Like Zn-Finger Domain.

Photosynthesis is performed by large complexes, composed of subunits encoded by the nuclear and chloroplast genomes. Assembly is assisted by general and target-specific chaperones, but their mode of action is yet unclear. We formerly showed that ZnJ2 is an algal chaperone resembling BSD2 from land plants.

'Speaking Kleinian': Susan Isaacs as Ursula Wise and the Inter-War Popularisation of Psychoanalysis.

How did the complex concepts of psychoanalysis become popular in early twentieth-century Britain? This article examines the contribution of educator and psychoanalyst Susan Isaacs (1885-1948) to this process, as well as her role as a female expert in the intellectual and medical history of this period. Isaacs was one of the most influential British psychologists of the inter-war era, yet historical research on her work is still limited. The article focuses on her writing as 'Ursula Wise', answering the questions of parents and nursery nurses in the popular journal Nursery World, from 1929 to 1936.

Interpersonal rivalries, gender and the intellectual and scientific making of psychoanalysis in 1940s Britain.

This article examines the 1940s debates regarding the status and professional orthodoxy of psychoanalysis following Sigmund Freud's death, by exploring the Anna Freud-Melanie Klein Controversial Discussions in the British Psychoanalytical Society. Focusing on the work of now-forgotten analysts Melitta Schmideberg and Edward Glover, and on their relationship with Klein and her supporters, the article reveals how these neglected, yet important, debates were complicated by interpersonal and professional ties, processes of the professionalization, and changing gender norms. Although historians of psychoanalysis have not ignored the jealousies, resentments, and complex relationships between psychoanalysts, these scholars often continue to view these as separate from the processes of creating science.

Transgene Expression in Microalgae-From Tools to Applications.

Microalgae comprise a biodiverse group of photosynthetic organisms that reside in water sources and sediments. The green microalgae Chlamydomonas reinhardtii was adopted as a useful model organism for studying various physiological systems. Its ability to grow under both photosynthetic and heterotrophic conditions allows efficient growth of non-photosynthetic mutants, making Chlamydomonas a useful genetic tool to study photosynthesis.

The eIF3 complex of Leishmania-subunit composition and mode of recruitment to different cap-binding complexes.

Eukaryotic initiation factor 3 (eIF3) is a multi-protein complex and a key participant in the assembly of the translation initiation machinery. In mammals, eIF3 comprises 13 subunits, most of which are characterized by conserved structural domains. The trypanosomatid eIF3 subunits are poorly conserved.

HSP33 in eukaryotes - an evolutionary tale of a chaperone adapted to photosynthetic organisms.

HSP33 was originally identified in bacteria as a redox-sensitive chaperone that protects unfolded proteins from aggregation. Here, we describe a eukaryote ortholog of HSP33 from the green algae Chlamydomonas reinhardtii, which appears to play a protective role under light-induced oxidizing conditions. The algal HSP33 exhibits chaperone activity, as shown by citrate synthase aggregation assays.

TGF-β1 induced transdifferentiation of rpe cells is mediated by TAK1.

Background And Aim: Proliferative vitreoretinopathy (PVR) is an active process that develops as a complication upon retinal detachment (RD), accompanied by formation of fibrotic tissue. The main cells involved in the development of fibrotic tissue during PVR are the retinal pigment epithelial (RPE) cells. The RPE cells undergo epithelial-mesenchymal transition (EMT) which leads to complex retinal detachment and loss of vision.

Serine protease inhibitors interact with IFN-γ through up-regulation of FasR; a novel therapeutic strategy against cancer.

Among the many immunomodulatory and anti-tumor activities, IFN-γ up-regulates tumor cell death mediated by Fas receptor (FasR). Our and several other studies have demonstrated the involvement of trypsin-like proteases (TLPs) in the mode of action of IFN-γ. In the present study, we tried to unravel the role of serine proteases in IFN-γ induced Fas-mediated cell death.

Development of a nuclear transformation system for Oleaginous Green Alga Lobosphaera (Parietochloris) incisa and genetic complementation of a mutant strain, deficient in arachidonic acid biosynthesis.

Microalgae are considered a promising source for various high value products, such as carotenoids, ω-3 and ω-6 polyunsaturated fatty acids (PUFA). The unicellular green alga Lobosphaera (Parietochloris) incisa is an outstanding candidate for the efficient phototrophic production of arachidonic acid (AA), an essential ω-6 PUFA for infant brain development and a widely used ingredient in the baby formula industry. Although phototrophic production of such algal products has not yet been established, estimated costs are considered to be 2-5 times higher than competing heterotrophic production costs.

The BSD2 ortholog in Chlamydomonas reinhardtii is a polysome-associated chaperone that co-migrates on sucrose gradients with the rbcL transcript encoding the Rubisco large subunit.

The expression of the CO2 -fixation enzyme ribulose-bisphosphate carboxylase/oxygenase (Rubisco), which is affected by light, involves the cysteine-rich protein bundle-sheath defective-2 (BSD2) that was originally identified in maize bundle-sheath cells. We identified the BSD2 ortholog in Chlamydomonas reinhardtii as a small protein (17 kDa) localized to the chloroplast. The algal BSD2-ortholog contains four CXXCXGXG DnaJ-like elements, but lacks the other conserved domains of DnaJ.

Regulation of autophagy by α1-antitrypsin: "a foe of a foe is a friend".

Autophagy is involved in both the cell protective and the cell death process but its mechanism is largely unknown. The present work unravels a novel intracellular mechanism by which the serpin α1-antitrypsin (AAT) acts as a novel negative regulator of autophagic cell death. For the first time, the role of intracellularly synthesized AAT, other than in liver cells, is demonstrated.

RNAthermsw: direct temperature simulations for predicting the location of RNA thermometers.

The mechanism of RNA thermometers is a subject of growing interest. Also known as RNA thermosensors, these temperature-sensitive segments of the mRNA regulate gene expression by changing their secondary structure in response to temperature fluctuations. The detection of RNA thermometers in various genes of interest is valuable as it could lead to the discovery of new thermometers participating in fundamental processes such as preferential translation during heat-shock.