787 research outputs found

    Biology and Molecular Biology of \u3ci\u3eIxodes scapularis\u3c/i\u3e

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    This chapter describes the biology of the tick Ixodes scapularis in relation to its role as the vector of the Lyme disease agent, Borrelia burgdorferi. Following a review of the internal anatomy of the tick, we review basic molecular processes that contribute to an understanding of the dynamics of the tick\u27s specialized parasitic processes, including attachment behavior, salivation; silencing of host anti-inflammatory responses to enable blood ingestion at the dermal feeding site; hemoglobin digestion and reproduction. The chapter is divided into three parts: 1) systematic and anatomical characteristics of ticks; 2) host finding, attachment, salivary disruption of host defenses, blood feeding and digestion; and 3) molecular regulation of tick bodily functions and reproduction. In the first part, we review the systematics of ticks and the taxonomic position of the vector of Lyme disease, I. scapularis, compared to other tick species. Next, we review the general organization of the tick body, including (a) the mouthparts essential for sucking blood, (b) the powerful sucking pharynx, (c) the midgut and its role in blood and hemoglobin digestion, (d) the salivary glands and their complex cellular organization, (e) the synganglion (a fused central nervous system) responsible for controlling all body functions, (f) the reproductive organs, and (g) the tracheal system that facilitates air intake and removal of CO2. In the second part, we highlight the role of the tick\u27s salivary glands in secreting a remarkably complex array of anti-hemostatic molecules that modulate the bite site in the host skin and how these salivary molecules facilitate the lengthy blood-sucking process. We also describe how ticks capture hemoglobin and internalize it in midgut epithelial cells for intracellular digestion, followed by the sequestration of heme into specialized hemosomes for disposal as hematin. We also will review the neural control of regulation of tick salivary glands, blood uptake, hemoglobin digestion, blood meal concentration, water/salt elimination, vitellogenesis and receptor mediated vitellogenin uptake in the developing oocytes and their oviposition

    Cryo-Electron Tomography Elucidates the Molecular Architecture of Treponema pallidum, the Syphilis Spirochete

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    Cryo-electron tomography (CET) was used to examine the native cellular organization of Treponema pallidum, the syphilis spirochete. T. pallidum cells appeared to form flat waves, did not contain an outer coat and, except for bulges over the basal bodies and widening in the vicinity of flagellar filaments, displayed a uniform periplasmic space. Although the outer membrane (OM) generally was smooth in contour, OM extrusions and blebs frequently were observed, highlighting the structure’s fluidity and lack of attachment to underlying periplasmic constituents. Cytoplasmic filaments converged from their attachment points opposite the basal bodies to form arrays that ran roughly parallel to the flagellar filaments along the inner surface of the cytoplasmic membrane (CM). Motile treponemes stably attached to rabbit epithelial cells predominantly via their tips. CET revealed that T. pallidum cell ends have a complex morphology and assume at least four distinct morphotypes. Images of dividing treponemes and organisms shedding cell envelope-derived blebs provided evidence for the spirochete’s complex membrane biology. In the regions without flagellar filaments, peptidoglycan (PG) was visualized as a thin layer that divided the periplasmic space into zones of higher and lower electron densities adjacent to the CM and OM, respectively. Flagellar filaments were observed overlying the PG layer, while image modeling placed the PG-basal body contact site in the vicinity of the stator–P-collar junction. Bioinformatics and homology modeling indicated that the MotB proteins of T. pallidum, Treponema denticola, and Borrelia burgdorferi have membrane topologies and PG binding sites highly similar to those of their well-characterized Escherichia coli and Helicobacter pylori orthologs. Collectively, our results help to clarify fundamental differences in cell envelope ultrastructure between spirochetes and gram-negative bacteria. They also confirm that PG stabilizes the flagellar motor and enable us to propose that in most spirochetes motility results from rotation of the flagellar filaments against the PG

    GEOLOGI DAN GEOMETRI LAPISAN BATUBARA ERAH JAWERA, DISTRIK TELUK ARGUNI BAWAKABUPATEN KAIMANA, PROVINSI PAPUA BARAT

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    Secara administratif, daerah telitian terletak di daerah Jawera, Distrik Teluk Arguni Bawah, Kabupaten Kaimana, Provinsi Papua Barat. Letak geografis 02 o 53’ 43,66” - 03 o 57’ 43,6” LS dan 133 o 37’ 30.8” - 133 o 39’ 32,4” BT, atau 347209 mE - 350964 mE dan 9672500 mN – 9667862 mN zona UTM -53 dengan luas wilayahnya adalah 18,241Km 2 . Metodologi yang dilakukan dalam penelitian ini terdiri dari tiga tahapan, yaitu: akuisisi, analisa, dan sintesa. Akuisisi merupakan tahapan perolehan data yang terdiri dari studi pustaka regional dan pemetaan geologi permukaan. Analisa merupakan tahapan pemrosesan data terhadap hal yang geometri lapisan batubara dan proses geologi di daerah telitian, dan tahapan sintesa adalah menjelaskan proses – proses geologi yang mempengaruhi kondisi geometri lapisan batubara. Berdasarkan aspek geomorfologi menurut Van Zuidam (1983), maka daerah telitian dapat dibagi menjadi 2 bentukan asal dan 3 satuan bentuklahan, yaitu: a. Bentukan asal struktural (S) terdiri dari satuan bentuklahan perbukitan struktural bergelombang sedang-lemah (S1) dan satuan bentuklahan perbukitan struktural berombak (S2). b. Bentukan asal fluvial (F), yaitu satuan bentuklahan dataran rawa (F1). Pola pengaliran yang berkembang pada daerah telitian yaitu trellis. Stratigrafi daerah telitian dari tua ke muda terdiri dari Satuan batulanau Steenkool, Satuan batupasir Steenkool, Satuan batulanau pembawa batubara Steenkool dan Satuan endapan aluvial. Daerah telitian merupakan sayap barat antiklin dengan struktur geologi yang berkembang berupa sesar mendatar kiri/Left Slip fault (Rickard,1972). Lingkungan pengendapan Formasi Steenkool pada daerah telitian adalah Tidal Flats dengan sub-lingkungan pengendapan supratidalsubtidalpada fasies salt marsh, mud flats dan mixed flats (Tucker, 1982). Geometri lapisan batubara salah satu aspek yang diperhitungkan dalam penentuan kebijakan eksplorasi selanjutnya. Menurut kuncoro ( 2000), geometri lapisan batubara terdiri merupakan aspek dimensi atau ukuran dari suatu lapisan batubara meliputi tebal, kemenerusan, kemiringan, pola sebaran, bentuk, keteraturan, pelapukan, cleat, dan kondisi roof dan floor lapisan batubara. Secara umum, geometri lapisan batubara di daerah penelitian dipengaruhi oleh proses geologi syn depositional – post depositional

    Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen

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    The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation 'the stealth pathogen'. Despite the many hurdles to studying syphilis pathogenesis, most notably the inability to culture and to genetically manipulate T. pallidum, in recent years, considerable progress has been made in elucidating the structural, physiological, and regulatory facets of T. pallidum pathogenicity. In this Review, we integrate this eclectic body of information to garner fresh insights into the highly successful parasitic lifestyles of the syphilis spirochete and related pathogenic treponemes

    CD14 Modulates PI3K/AKT/p38-MAPK Licensing of Negative Regulators of TLR Signaling to Restrain Chronic Inflammation

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    Current thinking emphasizes the primacy of CD14 in facilitating TLR recognition of microbes to initiate proinflammatory signaling events and the importance of p38-MAPK in augmenting such responses. Herein, this paradigm is challenged by demonstrating that recognition of _Borrelia burgdorferi_ not only triggers an inflammatory response in the absence of CD14, but one that is uncontrolled as a consequence of impaired PI3K/AKT/p38-MAPK signaling and negative regulation of TLR2. CD14 deficiency results in hyperphosphorylation of AKT and reduced activation of p38. Such aberrant signaling leads to decreased negative regulation by SOCS1, SOCS3, and CIS thereby engendering a more severe and persistent inflammatory response to _B. burgdorferi_. Perturbation of this CD14/p38-MAPK-dependent mechanism of immune regulation may underlie development of infectious chronic inflammatory syndromes

    Regulation of OspE-Related, OspF-Related, and Elp Lipoproteins of Borrelia burgdorferi Strain 297 by Mammalian Host-Specific Signals

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    This is the published version. Copyright 2001 by the American Society for Microbiology.In previous studies we have characterized the cp32/18 loci inBorrelia burgdorferi 297 which encode OspE and OspF orthologs and a third group of lipoproteins which possess OspE/F-like leader peptides (Elps). To further these studies, we have comprehensively analyzed their patterns of expression throughout the borrelial enzootic cycle. Serial dilution reverse transcription-PCR analysis indicated that although a shift in temperature from 23 to 37°C induced transcription for all nine genes analyzed, this effect was often markedly enhanced in mammalian host-adapted organisms cultivated within dialysis membrane chambers (DMCs) implanted within the peritoneal cavities of rats. Indirect immunofluorescence assays performed on temperature-shifted, in vitro-cultivated spirochetes and organisms in the midguts of unfed and fed ticks revealed distinct expression profiles for many of the OspE-related, OspF-related, and Elp proteins. Other than BbK2.10 and ElpA1, all were expressed by temperature-shifted organisms, while only OspE, ElpB1, OspF, and BbK2.11 were expressed in the midguts of fed ticks. Additionally, although mRNA was detected for all nine lipoprotein-encoding genes, two of these proteins (BbK2.10 and ElpA1) were not expressed by spirochetes cultivated in vitro, within DMCs, or by spirochetes within tick midguts. However, the observation that B. burgdorferi-infected mice generated specific antibodies against BbK2.10 and ElpA1 indicated that these antigens are expressed only in the mammalian host and that a form of posttranscriptional regulation is involved. Analysis of the upstream regions of these genes revealed several differences between their promoter regions, the majority of which were found in the −10 and −35 hexamers and the spacer regions between them. Also, rather than undergoing simultaneous upregulation during tick feeding, these genes and the corresponding lipoproteins appear to be subject to progressive recruitment or enhancement of expression as B. burgdorferi is transmitted from its tick vector to the mammalian host. These findings underscore the potential relevance of these molecules to the pathogenic events of early Lyme disease

    The Cross-Talk between Spirochetal Lipoproteins and Immunity

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    Spirochetal diseases such as syphilis, Lyme disease and leptospirosis are major threats to public health. However the immunopathogenesis of these diseases has not been fully elucidated. Spirochetes interact with the host through various structural components such as lipopolysaccharides (LPS), surface lipoproteins and glycolipids. Although spirochetal antigens such as LPS and glycolipids may contribute to the inflammatory response during spirochetal infections, spirochetes such as Treponema pallidum and Borrelia burgdorferi lack LPS. Lipoproteins are most abundant proteins that are expressed in all spirochetes and often determine how spirochetes interact with their environment. Lipoproteins are proinflammatory, may regulate responses from both innate and adaptive immunity and enable the spirochetes to adhere to the host or the tick midgut or to evade the immune system. However, most of the spirochetal lipoproteins have unknown function. Herein, the immunomodulatory effects of spirochetal lipoproteins are reviewed and are grouped into two main categories: effects related to immune evasion and effects related to immune activation. Understanding lipoprotein-induced immunomodulation will aid in elucidating innate immunopathogenesis processes and subsequent adaptive mechanisms potentially relevant to spirochetal disease vaccine development and to inflammatory events associated with spirochetal diseases
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