PacBio assembly of a Plasmodium knowlesi genome sequence with Hi-C correction and manual annotation of the SICAvar gene family.

Plasmodium knowlesi has risen in importance as a zoonotic parasite that has been causing regular episodes of malaria throughout South East Asia. The P. knowlesi genome sequence generated in 2008 highlighted and confirmed many similarities and differences in Plasmodium species, including a global view of several multigene families, such as the large SICAvar multigene family encoding the variant antigens known as the schizont-infected cell agglutination proteins. However, repetitive DNA sequences are the bane of any genome project, and this and other Plasmodium genome projects have not been immune to the gaps, rearrangements and other pitfalls created by these genomic features. Today, long-read PacBio and chromatin conformation technologies are overcoming such obstacles. Here, based on the use of these technologies, we present a highly refined de novo P. knowlesi genome sequence of the Pk1(A+) clone. This sequence and annotation, referred to as the 'MaHPIC Pk genome sequence', includes manual annotation of the SICAvar gene family with 136 full-length members categorized as type I or II. This sequence provides a framework that will permit a better understanding of the SICAvar repertoire, selective pressures acting on this gene family and mechanisms of antigenic variation in this species and other pathogens

A gramática e os conteúdos da percepção

This paper aims to critically discuss representationalist and anti-representationalist positions regarding perceptual experience—at the same time as it seeks to take a stand in favor of the former rather than the latter. Taking as starting point the so-called “McDowell-Travis Debate”, we intend to hold two possible notions of seeing as/seeing that to respond Travis’s anti-representationalist argument: on the one hand, McDowell’s idea that thinkables can figure as contents of perceptual experience; on the other, a phenomenological and Heideggerianproposal that takes the content of perceptual experience in terms of its meaning.O presente artigo tem o objetivo de discutir criticamente posições representacionistas e antirepresentacionistas no que se refere à experiência perceptual – ao mesmo tempo em que procura tomar posição em favor da primeira em detrimento da segunda. Tendo como ponto de partida o chamado “Debate entre John McDowell e Charles Travis”, pretendemos, no intuito de contornarmos as pressões antirepresentacionistas de Travis, defender aquelas que poderiam ser duas noções de ver como/que (seeing as/seeing that): de um lado, a ideia mcdowelliana de que conteúdos pensáveis (thinkables) podem figurar na experiência perceptual; de outro, uma proposta fenomenológica, que entende o conteúdo representacional da experiência perceptual em termos de seu significado

Possible mechanisms of allergy prevention: dendritic cells as regulators of the allergy-protective immune response induced by cowshed bacteria

Aktuelle epidemiologische Studien belegen, dass Kinder, die in einer bäuerlichen Umgebung aufwachsen, eine geringere Inzidenz für atopische Sensibilisierung, Heuschnupfen und Asthma aufweisen, als Kinder im selben Alter, die nicht in dieser Umgebung leben. Diese Befunde unterstützen die Hygiene-Hypothese, welche besagt, dass ein Kontakt zu einer Mikroorganismen-reichen Umgebung in den ersten Lebensjahren die Entwicklung von allergischen Reaktionen im späteren Leben beeinflusst. Da die ersten Lebensjahre wichtig für die Reifung des Immunsystems und der Entwicklung einer gesunden THelfer (TH)-Zell-Balance (TH1/TH2/TReg) sind, könnten die mikrobiellen Komponenten eine entscheidende Rolle bei der Ausrichtung diese Balance spielen, indem sie entweder TH1-Antworten begünstigen und dadurch die allergieassoziierte TH2-Antwort unterdrücken oder indem sie TReg-Antworten induzieren und damit generell alle überschießenden Immunantworten supprimieren. Daraus entstand die Frage, ob Mikroorgansimen der bäuerlichen Umgebung und/oder ihre Produkte in der Lage sind, die Immunantworten in einer dieser Weisen zu modulieren. Um die potentielle allergieprotektive Wirkung dieser Mikroorgansimen zu untersuchen, wurden zwei aus Kuhställen isolierte Bakterienstämme, Acinetobacter lwoffii F78 (A. lwoffii F78) und Lactococcus lactis G121 (L. lactis G121), ausgewählt und charakterisiert. Tatsächlich konnte in einem Mausmodell für allergisches Asthma gezeigt werden, dass beide Kuhstallisolate die allergischen Reaktionen der Mäuse reprimieren. Da unklar blieb, welche bakteriellen Moleküle und welche Rezeptoren und nachfolgenden Signaltransduktionswege beteiligt waren, wurde die Fähigkeit der Bakterien Immunantworten zu modulieren in humanen dendritischen Zellen (DCs) untersucht. Beide Bakterienstämme induzierten die Aktivierung und Reifung der DCs und führten zu einer stark TH1-polarisierten Immunantwort. Zudem konnten keine Anzeichen für die Induktion einer TH2- oder TReg- Antwort nachgewiesen werden. Um die für die TH1-Polarisierung verantwortlichen Strukturen der Bakterien näher zu charakterisieren wurde die Beteiligung verschiedener Rezeptoren des angeborenen Immunsystems untersucht. Diese Studien zeigten, dass der TLR4-Ligand von A. lwoffii F78, das LPS der äußeren Membran, für die TH1-polarisierenden Effekte verantwortlich ist und zumindest für die allergieprotektiven Fähigkeiten die bedeutendste Struktur dieses Bakterienstammes ist. Im Hinblick auf L. lactis G121 konnte die Notwendigkeit der zellulären Aufnahme des Bakteriums und damit die Involvierung eines intrazellulären Rezeptors, wahrscheinlich NOD2, für die TH1-polarisierenden Effekte nachgewiesen werden. Zudem induzierte L. lactis G121 eine untypische Zellkerntranslokation der NF-κB-Untereinheit c-Rel ohne gleichzeitige Translokation der p65- Untereinheit. Weiterhin konnte eine bis zu 48 h anhaltende Aktivierung der DCs durch L. lactis G121 festgestellt werden. Dies könnte ein wichtiger Mechanismus für eine dauerhafte Induktion einer anti-allergischen Immunantwort sein. Insgesamt untermauern diese Daten die Hygiene-Hypothese und implizieren dass die TH1- polarisierenden Eigenschaften der Bakterien wichtige Mechanismen für die allergieprotektiven Effekte der bäuerlichen Umgebung darstellen. Zudem liefert diese Arbeit erste Ansatzpunkte für die Entwicklung von allergieprotektiven Therapien mit einer potentiellen Anwendung der Kuhstallbakterien.Recent epidemiological studies clearly indicate that children who grow up in a farming environment show lower levels of atopic sensitization, hay fever and asthma than children of the same age living not in such an environment. These findings support the hygiene hypothesis, stating that an early-life contact to an environment rich in microbial compounds influences the development of allergic reactions later in life. As the first year of life is important for the maturation of the immune system and the establishment of the THelper (TH) cell balance (TH1/TH2/TReg) such microbial contact might play a pivotal role in adjusting this balance by either promoting TH1 responses and thereby inhibiting allergy-associated TH2 responses or promoting TRegs and thereby suppress in general overwhelming immune responses. Therefore the question arose if farm microbial organisms and/or their products may have the ability to modulate immune responses in either way. To gain further insight into the potential allergy-protective properties of farm microbes two bacterial species isolated from cowsheds of farms were selected and characterized, namely Acinetobacter lwoffii F78 (A. lwoffii F78) and Lactococcus lactis G121 (L. lactis G121). In fact, it could be shown that both bacterial isolates were able to reduce allergic reactions in a mouse model of allergic asthma. Since it remained unclear which bacterial molecules and which receptors and subsequent signal transduction pathways were involved, the immune modulatory capacities of the bacteria with focus on their influence on the TH cell balance were examined in human dendritic cells (DCs) as these cells provide a number of essential signals for T cell priming. Both bacterial strains induced activation and maturation of DCs and led to a strong TH1- polarizing immune response. Furthermore, no evidence for the induction of TH2 or TReg cells could be detected. To further characterize the microbial structures responsible for the allergyprotective properties the involvement of innate immune receptors that participated in recognition of the two bacteria strains was analyzed. These studies revealed that the TLR4 ligand from A. lwoffii F78, the LPS of the outer membrane is responsible for the TH1- polarizing effects of A. lwoffii F78 and, at least with respect to the allergy-protective properties, seems to be the most dominant structure of this strain. With respect to L. lactis G121, the requirement of phagocytic uptake and thus an intracellular receptor, which most likely is NOD2, could be shown for the TH1-polarizing effects. In addition, L. lactis G121 induced an atypical nuclear translocation of the NF-κB subunit c-Rel without translocation of the p65 subunit. Moreover, a sustained activation of DCs for up to 48 h was detected. This might be an important mechanism for a prolonged triggering of an anti-allergic immune response. Together, these data strongly support the hygiene hypothesis and imply that the TH1- polarization properties of the bacteria are important mechanisms for the allergy-protective farm effects. In addition, this work provides first starting points for the development of allergyprotective therapies with potential application of the cowshed bacteria

Discovery and assembly of repeat family pseudomolecules from sparse genomic sequence data using the Assisted Automated Assembler of Repeat Families (AAARF) algorithm

<p>Abstract</p> <p>Background</p> <p>Higher eukaryotic genomes are typically large, complex and filled with both genes and multiple classes of repetitive DNA. The repetitive DNAs, primarily transposable elements, are a rapidly evolving genome component that can provide the raw material for novel selected functions and also indicate the mechanisms and history of genome evolution in any ancestral lineage. Despite their abundance, universality and significance, studies of genomic repeat content have been largely limited to analyses of the repeats in fully sequenced genomes.</p> <p>Results</p> <p>In order to facilitate a broader range of repeat analyses, the Assisted Automated Assembler of Repeat Families algorithm has been developed. This program, written in PERL and with numerous adjustable parameters, identifies sequence overlaps in small shotgun sequence datasets and walks them out to create long pseudomolecules representing the most abundant repeats in any genome. Testing of this program in maize indicated that it found and assembled all of the major repeats in one or more pseudomolecules, including coverage of the major Long Terminal Repeat retrotransposon families. Both Sanger sequence and 454 datasets were appropriate.</p> <p>Conclusion</p> <p>These results now indicate that hundreds of higher eukaryotic genomes can be efficiently characterized for the nature, abundance and evolution of their major repetitive DNA components.</p

Untersuchungen zur Interaktion von Ipomoea batatas mit synergistischen und pathogenen Mikroorganismen

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MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades

O papel da função do juízo na intuição e o problema da generalidade para leituras conceitualistas de Kant

Este artigo pretende discutir criticamente as implicações exegéticas e filosóficas da adoção de uma posição conceitualista com relação à filosofia de Kant, no que diz respeito, mais especificamente, ao que seria o papel dos conceitos nas intuições. Ao afirmar que “a mesma função, que confere unidade às diversas representações num juízo, dá também unidade à mera síntese de representações diversas numa intuição” (KrV, A79/B104-5), Kant, de fato, abre espaço para uma leitura conceitualista. Contudo, pretendo mostrar que uma interpretação conceitualista esbarra tanto em problemas textuais quanto argumentativos. Tomando como ponto de partida o debate entre conceitualistas (McDowell 2009a; Land 2015) e não conceitualistas kantianos (Hanna, 2006; Allais, 2009; De Sa Pereiram, 2013; McLear, 2016), procuro mostrar que o envolvimento dos conceitos nas intuições teria como consequência um difícil problema filosófico, que vai além dos debates estritamente kantianos (Travis, 2018; Siegel, 2019): a saber, o de como a intuição, com sua natureza particular, poderia ao mesmo tempo abarcar um aspecto de generalidade próprio dos conceitos.This paper intends to critically discuss the exegetical and philosophical implications of adopting a conceptualist position on Kant’s philosophy, with regard, more specifically, to the role of concepts in intuitions. In saying that “The same function which gives unity to the various representations in a judgment also gives unity to the mere synthesis of different representations in an intuition” (KrV, A79/B104-5), Kant, in fact, opens up space for a conceptualist reading. However, I intend to show that a conceptualist interpretation faces both textual and argumentative problems. Taking as a starting point the debate between Kantian conceptualists (McDowell, 2009a; Land, 2015) and non-conceptualists (Hanna, 2006; Allais, 2009; De Sa Pereira, 2013; McLear, 2016), I seek to show that the involvement of concepts in intuitions would result in a philosophical problem that goes beyond the Kantian debate (Travis, 2018; Siegel, 2019): namely, that of how intuition, with its particular nature, could at the same time encompass an aspect of generality typical of concepts

The Selaginella Genome Identifies Genetic Changes Associated with the Evolution of Vascular Plants

Vascular plants appeared ~410 million years ago then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes (1). We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first non-seed vascular plant genome reported. By comparing gene content in evolutionary diverse taxa, we found that the transition from a gametophyte- to sporophyte- dominated life cycle required far fewer new genes than the transition from a non-seed vascular to a flowering plant, while secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in post- transcriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the tasiRNA pathway and extensive RNA editing of organellar genes