Buddhist Philosophy of Logic

Logic in Buddhist Philosophy concerns the systematic study of anumāna (often translated as inference) as developed by Dignāga (480-540 c.e.) and Dharmakīti (600-660 c.e.). Buddhist logicians think of inference as an instrument of knowledge (pramāṇa) and, thus, logic is considered to constitute part of epistemology in the Buddhist tradition. According to the prevalent 20th and early 21st century ‘Western’ conception of logic, however, logical study is the formal study of arguments. If we understand the nature of logic to be formal, it is difficult to see what bearing logic has on knowledge. In this paper, by weaving together the main threads of thought that are salient in Dignāga’s and Dharmakīti’s texts, I shall re-conceive the nature of logic in the context of epistemology and demarcate the logical part of epistemology which can be recognised as logic. I shall demonstrate that we can recognise the logical significance of inference as understood by Buddhist logicians despite the fact that its logical significance lies within the context of knowledge

The compaction of nucleoids in barley chloroplasts (Hordeum vulgare L.) by WHIRLY1

In den Plastiden liegt die DNA (ptDNA) in Form von DNA-Protein-Strukturen vor, die in Anlehnung an die Organisation bakterieller DNA als Nukleoide bezeichnet werden. Ein abundantes Protein plastidärer Nukleoide Höherer Pflanzen ist WHIRLY1. In der vorliegenden Arbeit wurde das WHIRLY1-Protein der Gerste (HvWHIRLY1) als Kompaktierungsprotein für die Nukleoide in jungen und ausdifferenzierten Chloroplasten identifiziert. Untersuchungen zur Nukleoidmorphologie in transgenen Gerstenlinien, in denen die Menge an HvWHIRLY1 durch RNAi reduziert ist, zeigten, dass eine Teilpopulation der Nukleoide im Vergleich zu den Nukleoiden des Wildtyps deutlich vergrößert ist und damit einhergehend einen verringerten Kompaktierungsgrad aufweist. Die kompaktierende Wirkung des HvWHIRLY1-Proteins auf die Nukleoide wurde außerdem mit heterologen Expressionsstudien in E. coli bestätigt. Auch das WHIRLY1-Protein des Maises bewirkt eine stärkere Verpackung der bakteriellen Nukleoide, während die plastidären WHIRLY-Proteine von Arabidopsis diese Funktion nicht besitzen. Die Wirkung als Kompaktierungsprotein ist auf ein kurzes Motiv am N-Terminus der monokotylen WHIRLY1-Proteine, das PRAPP-Motiv, zurückzuführen, das ausschließlich in den WHIRLY1-Proteinen aus der Familie der Poaceae zu finden ist. Die transgenen WHIRLY1-RNAi-Linien weisen zudem einen erhöhten Gehalt an ptDNA in ausdifferenzierten Chloroplasten auf, was auf eine erhöhte Replikationsaktivität hinweist. HvWHIRLY1 scheint die Replikation über die Nukleoidverpackung, welche die Zugänglichkeit der ptDNA für die Replikationsmaschinerie beeinflusst, zu steuern. Im Wildtyp sowie in den transgenen WHIRLY1-RNAi-Linien unterliegt die HvWHIRLY1-Proteinmenge entwicklungs- und umweltabhängigen Schwankungen. Die lichtinduzierte Reduktion des HvWHIRLY1-Proteins führt in den transgenen WHIRLY1-RNAi-Linien zu photooxidativem Stress. Das HvWHIRLY1-Protein scheint daher auch eine Rolle bei der Anpassung der Pflanze an Stressbedingungen zu spielen.The DNA of plastids (ptDNA) is organized as DNA-protein-structures, which were designated as nucleoids with regard to bacterial nucleoids. An abundant protein of plastid nucleoids in higher plants is WHIRLY1. In the present work the WHIRLY1 protein of barley (HvWHIRLY1) was identified as a nucleoid compacting protein in young and mature chloroplasts. The investigation of the nucleoid morphology in transgenic barley lines, that have an RNAi-mediated reduction of the HvWHIRLY1 protein level, revealed that a subpopulation of nucleoids is enlarged and less condensed in comparison to wild type nucleoids. Heterologous expression of HvWHIRLY1 in E. coli confirmed that the HvWHIRLY1 protein has a function in compacting nucleoids. As well the WHIRLY1 protein of maize leads to an enhanced packaging of bacterial nucleoids, whereas plastid WHIRLY proteins of Arabidopsis have no impact on nucleoid compaction. The nucleoid compacting WHIRLY1 proteins in the family of Poaceae have a short N-terminal motif, the PRAPP-motif. These findings indicate functional differences between plastid WHIRLY proteins of monocots and dicots. Moreover, the transgenic WHIRLY1-RNAi lines contain an enhanced ptDNA content in mature chloroplasts indicating an enhanced plastid replication activity. By its impact on the structure of nucleoids HvWHIRLY1 seems to regulate the accessibility of ptDNA to the replication machinery of plastids. Accumulation of the HvWHIRLY1 protein depends on development-dependent and environment-dependent cues both in the wild type and the transgenic WHIRLY1-RNAi lines. The light-induced reduction of the HvWHIRLY1 protein leads to photooxidative stress in the transgenic WHIRLY1-RNAi lines. Therefore, the HvWHIRLY1 protein seems to play a role in plant acclimation to stress conditions

Expression des Protoonkogens Ets2 in Plattenepithelkarzinomen des Kopf- und Halsbereiches: Eine immunhistochemische Untersuchung

Die grundlegende Fragestellung der vorliegenden Untersuchung ist, in welchem Ausmaß das Onkoprotein Ets2 mittels immunhistochemischer Färbung in Plattenepithelkarzinomen des Kopf-Halsbereiches nachweisbar ist und ob ein Zusammenhang zwischen Expressionsgrad, den tumorspezifischen Charakteristika der TNM-Klassifikation und dem Alter bzw. Geschlecht der Patienten hergestellt und somit eine prognostische Aussage für den Patienten getroffen werden kann. Dazu wurden 141 formalinfixierte, in Paraffin eingebettete Gewebeproben aus Plattenepithelkarzinomen sowie 27 Gewebeproben gesunder Mukosa aus Mundhöhle, Oro- und Hypopharynx untersucht. In 92 der 141 Tumoren wurde Ets2 überexprimiert nachgewiesen, davon zeigten 10 Schnitte eine starke Färbung, 31 eine deutliche und 51 eine geringe Färbung. In Gewebeproben gesunder Mukosa wurde Ets2 nicht nachgewiesen. Es konnte keine signifikante Korrelation zwischen Ets2 – Expression und Alter bzw. Geschlecht der Patienten und den tumorspezifischen Charakteristika dargestellt werden. In Studien zu Plattenepithelkarzinomen des oberen Aerodigestivtraktes und des Cervix uteri sowie weiteren Tumorentitäten wie Karzinomen der Mamma, Prostata und der Glandula thyroidea konnte die Beteiligung von Ets2 an Tumorentstehung, Invasion und Metastasierung nachgewiesen werden. In diesen Studien konnte, wie in der vorliegenden Untersuchung kein statistischer Zusammenhang zwischen Ets2 und den pathologischen Faktoren der Tumore wie Stadium, Nodalstatus und Metastasierung dargestellt werden. Eine grundlegende Unterscheidung zwischen benignem und maligne verändertem Gewebe konnte in allen Untersuchungen anhand der Expression von Ets2 vorgenommen werden. Eine weitere für den Therapieverlauf entscheidende prognostische Aussage kann nicht getroffen werden. Folglich konnte Ets2 als potentieller Tumormarker für Plattenepithelkarzinome des Kopf – Halsbereiches in der vorliegenden Untersuchung nicht bestätigt werden

Dynamic composition, shaping and organization of plastid nucleoids

In this article recent progress on the elucidation of the dynamic composition and structure of plastid nucleoids is reviewed from a structural perspective. Plastid nucleoids are compact structures of multiple copies of different forms of ptDNA, RNA, enzymes for replication and gene expression as well as DNA binding proteins. Although early electron microscopy suggested that plastid DNA is almost free of proteins, it is now well established that the DNA in nucleoids similarly as in the nuclear chromatin is associated with basic proteins playing key roles in organization of the DNA architecture and in regulation of DNA associated enzymatic activities involved in transcription, replication, and recombination. This group of DNA binding proteins has been named plastid nucleoid associated proteins (ptNAPs). Plastid nucleoids are unique with respect to their variable number, genome copy content and dynamic distribution within different types of plastids. The mechanisms underlying the shaping and reorganization of plastid nucleoids during chloroplast development and in response to environmental conditions involve posttranslational modifications of ptNAPs, similarly to those changes known for histones in the eukaryotic chromatin, as well as changes in the repertoire of ptNAPs, as known for nucleoids of bacteria. Attachment of plastid nucleoids to membranes is proposed to be important not only for regulation of DNA availability for replication and transcription, but also for the coordination of photosynthesis and plastid gene expression

Genome communication in plants mediated by organelle-n-ucleus-located proteins

An increasing number of eukaryotic proteins have been shown to have a dual localization in the DNA-containing organelles, mitochondria and plastids, and/or the nucleus. Regulation of dual targeting and relocation of proteins from organelles to the nucleus offer the most direct means for communication between organelles as well as organelles and nucleus. Most of the mitochondrial proteins of animals have functions in DNA repair and gene expression by modelling of nucleoid architecture and/or chromatin. In plants, such proteins can affect replication and early development. Most plastid proteins with a confirmed or predicted second location in the nucleus are associated with the prokaryotic core RNA polymerase and are required for chloroplast development and light responses. Few plastid-nucleus-located proteins are involved in pathogen defence and cell cycle control. For three proteins, it has been clearly shown that they are first targeted to the organelle and then relocated to the nucleus, i.e. the nucleoid-associated proteins HEMERA and Whirly1 and the stroma-located defence protein NRIP1. Relocation to the nucleus can be experimentally demonstrated by plastid transformation leading to the synthesis of proteins with a tag that enables their detection in the nucleus or by fusions with fluoroproteins in different experimental set-ups. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'

Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B <em>Streptococcus</em>

ABSTRACT: Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophillic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens. KEY MESSAGE: Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-014-1157-y) contains supplementary material, which is available to authorized users

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Siglecg Limits the Size of B1a B Cell Lineage by Down-Regulating NFκB Activation

BACKGROUND: B1 B cells are believed to be a unique lineage with a distinct developmental pathway, function and activation requirement. How this lineage is genetically determined remained largely obscure. METHODS AND PRINCIPAL FINDINGS: Using the Siglecg-deficient mice with a knockin of green-fluorescent protein encoding sequence, we show here that, although the Siglecg gene is broadly expressed at high levels in all stages and/or lineages of B cells tested and at lower levels in other lineages, its deletion selectively expanded the B1a B cell lineages, including the frequency of the B1 cell progenitor in the bone marrow and the number of B1a cells in the peritoneal cavity, by postnatal expansion. The expansion of B1a B cells in the peritoneal correlated with enhanced activation of NFkappaB and was ablated by an IKK inhibitor. CONCLUSION AND SIGNIFICANCE: Our data revealed a critical role for Siglec G-NFkappaB pathway in regulating B1a B cell lineage. These data lead to a novel model of B1a lineage development that explains a large array of genetic data in this field

Human Papillomavirus Type 16 E5 Protein as a Therapeutic Target

Cervical cancer is a progressive disease with an onset of one to two decades on average. During the productive replication stage, the Human papillomavirus (HPV) genome is maintained episomally in the infected cervical epithelium and early gene products, including E5, are expressed. Therefore, E5 has a potential to contribute to the HPV-associated carcinogenic process. In invasive malignancies, the HPV genomes are commonly integrated into the host genome, and E6 and E7 genes remain intact. However, the E5 is lost or, if present, under-expressed as compared with the E6 and E7 proteins. This suggests that E5 may play a critical role in the genesis of cervical cancer but less of a role in its persistence or progression. In the initiation of neoplasia and the premalignant stage, there are fewer malignant cells than in the invasive malignancies. Moreover, cells in the invasive malignant stage are found to have a very low level of MHC class I and II, which could hamper the presentation of the antigen and lead to a decreased immune response. Since the E5 protein is likely to play a role during the early tumorigenesis stage, a therapeutic vaccine to target and eliminate the E5-expressing cells may be a good strategy to prevent premalignant lesions from progressing toward invasive cervical cancers. This paper provides an overview of HPV-induced cervical carcinogenesis and strategies for designing prophylactic and therapeutic vaccines to prevent and cure the cervical cancer. In particular, focus will be on the rationale of targeting the E5 protein to develop therapeutic vaccines