465 research outputs found

    HUBUNGAN ANTARA JUMLAH CD4 DAN KADAR HEMOGLOBIN PASIEN HIV

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    Latar belakang: Molekul CD4 merupakan penanda utama limfosit T helper. Pemeriksaan kadar CD4 rutin dilakukan pada pasien HIV untuk evaluasi perkembangan penyakit. HIV menurunkan jumlah CD4 menyebabkan penurunan kadar hemoglobin melalui aktivasi gen pro–apoptosis (karena penurunan jumlah CD4 dan peningkatan jumlah monosit) dan pemberian anti retroviral (zidovudin).Metode: Penelitian ini menggunakan metode cross–sectional. Hasil pemeriksaan laboratorium pasien HIV di poli HIV dan rawat inap RSUP Dr. Kariadi Semarang periode Juni–September 2017 dicatat. Kriteria eksklusi yaitu riwayat transfusi, perdarahan, keganasan, defisiensi (Fe, asam folat dan B12), penyakit metabolik dan autoimun. Kriteria inklusi yaitu pasien positif HIV usia 18 sampai 60 tahun. Dilakukan telaah dokumen rekam medis responden sebanyak 34 pasien yang belum mendapat terapi ARV, 34 pasien yang sudah mendapat terapi ARV. Pemeriksaan CD4 menggunakan BD FACS Count (metode flowcytometry), kadar hemoglobin menggunakan Sapphire (metode fotometry). Analisis data menggunakan uji Spearman. Signifikansi dicapai jika p<0,05.Hasil: Analisis menunjukkan hubungan lemah positif signifikan antara jumlah CD4 dan kadar hemoglobin pada pasien HIV yang belum mendapat terapi ARV (r= 0,349; p = 0,043), yang sudah mendapat terapi ARV menunjukkan hubungan sedang positif signifikan (r = 0,452; p = 0,007). Keseluruhan kelompok menunjukkan hubungan sedang positif signifikan (r = 0,581; p = <0,001).Simpulan: Terdapat hubungan sedang positif signifikan antara jumlah CD4 dan kadar Hb pada pasien HIV.

    Simultaneous whole-animal 3D-imaging of neuronal activity using light field microscopy

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    3D functional imaging of neuronal activity in entire organisms at single cell level and physiologically relevant time scales faces major obstacles due to trade-offs between the size of the imaged volumes, and spatial and temporal resolution. Here, using light-field microscopy in combination with 3D deconvolution, we demonstrate intrinsically simultaneous volumetric functional imaging of neuronal population activity at single neuron resolution for an entire organism, the nematode Caenorhabditis elegans. The simplicity of our technique and possibility of the integration into epi-fluoresence microscopes makes it an attractive tool for high-speed volumetric calcium imaging.Comment: 25 pages, 7 figures, incl. supplementary informatio

    Drug discovery: A jump-start for electroceuticals

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    Imagine a day when electrical impulses are a mainstay of medical treatment. Your clinician will administer electroceuticals that target individual nerve fibres or specific brain circuits to treat an array of conditions. These will modulate the neural impulses that control the body, repair lost function and reinstate a healthy balance. They could coax insulin from islet cells, regulate food intake, and control inflammation. They may treat pressing major ailments such as hypertension, diabetes, obesity, heart failure, pulmonary and vascular disease. All this is within reach, we argue, if researchers from disparate disciplines in academia and industry work together. We herewith outline what needs to be done to bring about electroceuticals, and unveil a public-private research initiative and award that aim to catalyse the field

    Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

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    The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

    Transcriptomics reveal an integrative role for maternal thyroid hormones during zebrafish embryogenesis

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    Thyroid hormones (THs) are essential for embryonic brain development but the genetic mechanisms involved in the action of maternal THs (MTHs) are still largely unknown. As the basis for understanding the underlying genetic mechanisms of MTHs regulation we used an established zebrafish monocarboxylic acid transporter 8 (MCT8) knock-down model and characterised the transcriptome in 25hpf zebrafish embryos. Subsequent mapping of differentially expressed genes using Reactome pathway analysis together with in situ expression analysis and immunohistochemistry revealed the genetic networks and cells under MTHs regulation during zebrafish embryogenesis. We found 4,343 differentially expressed genes and the Reactome pathway analysis revealed that TH is involved in 1681 of these pathways. MTHs regulated the expression of core developmental pathways, such as NOTCH and WNT in a cell specific context. The cellular distribution of neural MTH-target genes demonstrated their cell specific action on neural stem cells and differentiated neuron classes. Taken together our data show that MTHs have a role in zebrafish neurogenesis and suggest they may be involved in cross talk between key pathways in neural development. Given that the observed MCT8 zebrafish knockdown phenotype resembles the symptoms in human patients with Allan-Herndon-Dudley syndrome our data open a window into understanding the genetics of this human congenital condition.Portuguese Fundacao para Ciencia e Tecnologia (FCT) [PTDC/EXPL/MARBIO/0430/2013]; CCMAR FCT Plurianual financing [UID/Multi/04326/2013]; FCT [SFRH/BD/111226/2015, SFRH/BD/108842/2015, SFRH/BPD/89889/2012]; FCT-IF Starting Grant [IF/01274/2014]info:eu-repo/semantics/publishedVersio

    The secreted triose phosphate isomerase of Brugia malayi is required to sustain microfilaria production in vivo

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    Human lymphatic filariasis is a major tropical disease transmitted through mosquito vectors which take up microfilarial larvae from the blood of infected subjects. Microfilariae are produced by long-lived adult parasites, which also release a suite of excretory-secretory products that have recently been subject to in-depth proteomic analysis. Surprisingly, the most abundant secreted protein of adult Brugia malayi is triose phosphate isomerase (TPI), a glycolytic enzyme usually associated with the cytosol. We now show that while TPI is a prominent target of the antibody response to infection, there is little antibody-mediated inhibition of catalytic activity by polyclonal sera. We generated a panel of twenty-three anti-TPI monoclonal antibodies and found only two were able to block TPI enzymatic activity. Immunisation of jirds with B. malayi TPI, or mice with the homologous protein from the rodent filaria Litomosoides sigmodontis, failed to induce neutralising antibodies or protective immunity. In contrast, passive transfer of neutralising monoclonal antibody to mice prior to implantation with adult B. malayi resulted in 60–70% reductions in microfilarial levels in vivo and both oocyte and microfilarial production by individual adult females. The loss of fecundity was accompanied by reduced IFNγ expression by CD4+ T cells and a higher proportion of macrophages at the site of infection. Thus, enzymatically active TPI plays an important role in the transmission cycle of B. malayi filarial parasites and is identified as a potential target for immunological and pharmacological intervention against filarial infections

    Telomeric expression sites are highly conserved in trypanosoma brucei

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    Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology
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