Chromerid genomes reveal the evolutionary path from photosynthetic algae to obligate intracellular parasites

The eukaryotic phylum Apicomplexa encompasses thousands of obligate intracellular parasites of humans and animals with immense socio-economic and health impacts. We sequenced nuclear genomes of Chromera velia and Vitrella brassicaformis, free-living non-parasitic photosynthetic algae closely related to apicomplexans. Proteins from key metabolic pathways and from the endomembrane trafficking systems associated with a free-living lifestyle have been progressively and non-randomly lost during adaptation to parasitism. The free-living ancestor contained a broad repertoire of genes many of which were repurposed for parasitic processes, such as extracellular proteins, components of a motility apparatus, and DNA- and RNA-binding protein families. Based on transcriptome analyses across 36 environmental conditions, Chromera orthologs of apicomplexan invasion-related motility genes were co-regulated with genes encoding the flagellar apparatus, supporting the functional contribution of flagella to the evolution of invasion machinery. This study provides insights into how obligate parasites with diverse life strategies arose from a once free-living phototrophic marine alga

Biomarqueurs des pathologies neurodégénératives dans le diagnostic des troubles cognitifs - Revue et recommandations de Swiss Memory Clinics [Biomarkers for the diagnosis of cognitive impairment - Recommendations from the Swiss Memory Clinics]

Established cerebrospinal fluid (CSF) biomarkers allow for earlier and more accurate etiological diagnosis of cognitive impairment. Information and counselling are needed both before and after biomarker-supported diagnosis. The procedures for diagnostic lumbar punctures and pre-analytical sample handling should follow published consensus recommendations. The results must be interpreted in the context of the other available history information and assessments. Blood-based biomarkers and other non-invasive markers are expected to become available for clinical practice soon. Consequently, a broader usage of biomarkers is expected and may accelerate the development of individually tailored prevention and treatment approaches. This article provides the recommendations of the Swiss Memory Clinics for the use of biomarkers in clinical practice

Biomarker in der Diagnostik kognitiver Störungen – Empfehlungen der Swiss Memory Clinics [Biomarkers for the diagnosis of cognitive impairment - Recommendations from the Swiss Memory Clinics]

Biomarkers for the diagnosis of cognitive impairment - Recommendations from the Swiss Memory Clinics Abstract. Molecular cerebrospinal fluid (CSF) biomarkers of neurodegenerative diseases are now part of the established diagnostic tools for the clinical investigation of cognitive disorders in the elderly. Biomarkers allow for earlier and more accurate differential diagnosis, and are recommended by the Swiss Memory Clinics as an additional investigation based upon individual indication. Information and counselling are needed both before and after biomarker-supported diagnosis. The procedures for diagnostic lumbar punctures and pre-analytical sample handling should follow published recommendations. The results must be interpreted in the context of the other available history and assessment outcome. Thanks to recent research progress, blood-based biomarkers and other non-invasive markers are expected to become available for clinical practice in the near future. This trend will likely lead to a much broader utilisation of biomarkers and may accelerate the development of effective and individually tailored prevention and treatment approaches. This review article provides an overview over the current state of biomarkers and provides the recommendations of the Swiss Memory Clinics for their use in clinical practice

Biomarqueurs des pathologies neurodégénératives dans le diagnostic des troubles cognitifs. Revue et recommandations de Swiss Memory Clinics

Established cerebrospinal fluid (CSF) biomarkers allow for earlier and more accurate etiological diagnosis of cognitive impairment. Information and counselling are needed both before and after biomarker-supported diagnosis. The procedures for diagnostic lumbar punctures and pre-analytical sample handling should follow published consensus recommendations. The results must be interpreted in the context of the other available history information and assessments. Blood-based biomarkers and other non-invasive markers are expected to become available for clinical practice soon. Consequently, a broader usage of biomarkers is expected and may accelerate the development of individually tailored prevention and treatment approaches. This article provides the recommendations of the Swiss Memory Clinics for the use of biomarkers in clinical practice. = Les marqueurs du liquide céphalorachidien établis permettent un diagnostic des troubles cognitifs plus précoce et précis. Il est nécessaire de conseiller les patients avant et après un examen des biomarqueurs. Les procédures de la ponction lombaire et de traitement préanalytique des échantillons doivent suivre des recommandations publiées. L’interprétation des résultats prendra en compte les antécédents médicaux et les autres résultats d’examen disponibles. Des marqueurs sanguins pourraient être disponibles dans un avenir proche. Cela pourrait conduire à une utilisation plus large des biomarqueurs et accélérer le développement d’approches personnalisées de prévention et de traitement. Cet article présente les recommandations de Swiss Memory Clinics concernant l’utilisation des biomarqueurs en pratique clinique

Biomarker in der Diagnostik kognitiver Störungen – Empfehlungen der Swiss Memory Clinics

Zusammenfassung. Molekulare Liquormarker der Alzheimer-Kernpathologie (Amyloidpathologie, Tau-Hyperphosphorylierung und neuronaler Zelluntergang) sind Bestandteil des diagnostischen Instrumentariums zur Abklärung kognitiver Störungen im Alter. Sie erlauben eine frühere und präzisere Diagnose und werden von Swiss Memory Clinics als Zusatzdiagnostik nach individuell gestellter Indikation empfohlen. Aufklärung und Beratung sind sowohl vor als auch nach der Biomarker-Diagnostik erforderlich. Die Durchführung der diagnostischen Lumbalpunktion und der präanalytische Umgang mit den Proben richtet sich nach publizierten Standards. Die Interpretation der Resultate muss sorgfältig und im Gesamtkontext aller anderen Befunde erfolgen. Dank bedeutender Fortschritte ist zu erwarten, dass Blutbiomarker und andere kostengünstige und leicht zugängliche Marker sowie spezifische Biomarker für weitere Demenzursachen in wenigen Jahren zur Verfügung stehen werden. Dieser Trend dürfte zu einem deutlich breiteren Einsatz von Biomarkern führen und die Entwicklung wirksamer und personalisiert anwendbarer Präventions- und Behandlungsansätze beschleunigen. Unser Beitrag bietet einen Überblick über den Stand der Entwicklung und beinhaltet Empfehlungen der Swiss Memory Clinics zum Einsatz von Liquormarkern im diagnostischen Prozess. Biomarkers for the diagnosis of cognitive impairment – Recommendations from the Swiss Memory Clinics Abstract. Molecular cerebrospinal fluid (CSF) biomarkers of neurodegenerative diseases are now part of the established diagnostic tools for the clinical investigation of cognitive disorders in the elderly. Biomarkers allow for earlier and more accurate differential diagnosis, and are recommended by the Swiss Memory Clinics as an additional investigation based upon individual indication. Information and counselling are needed both before and after biomarker-supported diagnosis. The procedures for diagnostic lumbar punctures and pre-analytical sample handling should follow published recommendations. The results must be interpreted in the context of the other available history and assessment outcome. Thanks to recent research progress, blood-based biomarkers and other non-invasive markers are expected to become available for clinical practice in the near future. This trend will likely lead to a much broader utilisation of biomarkers and may accelerate the development of effective and individually tailored prevention and treatment approaches. This review article provides an overview over the current state of biomarkers and provides the recommendations of the Swiss Memory Clinics for their use in clinical practice. Les biomarqueurs dans le diagnostic des troubles cognitifs – Recommandation de Swiss Memory Clinics Résumé. Les biomarqueurs moléculaires du liquide céphalorachidien (LCR) de la pathologie de la maladie d’Alzheimer font désormais partie des outils diagnostiques établis pour l’investigation clinique des troubles cognitifs chez les personnes âgées. Les biomarqueurs permettent un diagnostic différentiel plus précoce et plus précis et sont recommandés par Swiss Memory Clinics en tant qu’examen complémentaire sur la base d’une indication individuelle. Il est indispensable que la situation soit éclaircie et soigneusement discutée avant et après un examen des biomarqueurs. Les procédures de ponction lombaire diagnostique et de manipulation pré-analytique des échantillons doivent en outre suivre les recommandations publiées. L’interprétation des résultats doit prendre en compte les antécédents médicaux et les autres résultats d’examens disponibles. Grâce aux progrès récents, des biomarqueurs sanguins et d’autres marqueurs non-invasifs pourraient être disponibles pour la pratique clinique dans un avenir proche. Cela pourrait conduire à une utilisation beaucoup plus large des biomarqueurs et devrait accélérer le développement d’approches de prévention et de traitement efficaces et personnalisées. Cet article de synthèse offre un aperçu de l’état des lieux des biomarqueurs et présente les recommandations de Swiss Memory Clinics concernant leur utilisation en pratique clinique

Characterization of the small exported Plasmodium falciparum membrane protein SEMP1.

Survival and virulence of the human malaria parasite Plasmodium falciparum during the blood stage of infection critically depend on extensive host cell refurbishments mediated through export of numerous parasite proteins into the host cell. The parasite-derived membranous structures called Maurer's clefts (MC) play an important role in protein trafficking from the parasite to the red blood cell membrane. However, their specific function has yet to be determined. We identified and characterized a new MC membrane protein, termed small exported membrane protein 1 (SEMP1). Upon invasion it is exported into the RBC cytosol where it inserts into the MCs before it is partly translocated to the RBC membrane. Using conventional and conditional loss-of-function approaches we showed that SEMP1 is not essential for parasite survival, gametocytogenesis, or PfEMP1 export under culture conditions. Co-IP experiments identified several potential interaction partners, including REX1 and other membrane-associated proteins that were confirmed to co-localize with SEMP1 at MCs. Transcriptome analysis further showed that expression of a number of exported parasite proteins was up-regulated in SEMP1-depleted parasites. By using Co-IP and transcriptome analysis for functional characterization of an exported parasite protein we provide a new starting point for further detailed dissection and characterisation of MC-associated protein complexes

Localization of potential SEMP1 interacting proteins.

<p>Immunofluorescence assays of MeOH-fixed RBCs infected with 3D7 expressing SEMP1/PF3D7_0702500/PF3D7_0601900 with a C-terminal 3xHA tag and 3D7 expressing PIESP2 with a C-terminal GFP-tag, co-labelled with mouse α-SEMP1 and rat α-HA (PF3D7_0702500-3xHA & PF3D7_0601900-3xHA) /α-GFP (PIESP2-GFP). For co-labelling of SEMP1-3xHA with REX1 and Pf332, rat α-HA and rabbit α-REX1 / mouse α-Pf332 antibodies were used.</p

SEMP1 expression and localization.

<p>A: schematic representation of the <i>semp1</i> gene (top) and SEMP1 protein structure (bottom). TM, transmembrane protein. B: Live cell imaging of 3D7 parasites expressing SEMP1 with C-terminal tagged GFP. C: Immunofluorescence assays of MeOH-fixed RBCs infected with 3D7 expressing SEMP1 with a C-terminal 3xHA tag, co-labelled with rat α-HA and either rabbit α-MAHRP1 or rabbit α-REX1 antibodies. D: Scatter plot of co-localization of SEMP1 and REX1 in SEMP1-3xHA parasites. E: Electron microscopy (EM) of RBCs infected with 3D7 expressing SEMP1 with a C-terminal GFP tag labelled with rabbit α-GFP antibodies and decorated with 5 nm gold conjugated Protein A.</p

Conditional Knockdown of SEMP1.

<p>A: <i>EcoR</i>I-digested gDNA isolated from SEMP1-DD parasites (DD) was analysed by Southern blot and probed with radioactively labelled <i>hdhfr</i> B: A culture of 3D7 parasites expressing SEMP1-DD was split and cultured for 2 weeks in presence (Shld +) or absence (Shld -) of the small molecule Shield-1. Whole parasite-lysates were generated after saponin lysis and analysed by Western blot using α-SEMP1. As a loading control the blot was additionally probed with antibodies against the housekeeping protein GAPDH.</p