25 research outputs found

    Ddt Resistance in Anopheles Koliensis (Diptera: Culicidae) From Northeastern Irian Jaya, Indonesia

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    Nyamuk Anopheles koliensis, adalah perantara (vektor) penyakit malaria yang penting di daerah pedalaman Irian Jaya, Indonesia, yang telah dievaluasi kerentanannya terhadap DDT dengan menggunakan test kit diagnostik dan kertas yang telah diresapi sesuai dengan standar WHO. Serangkaian tes telah dilakukan di ARSO PIR I, yang merupakan tempat pemukiman para transmigran yang terletak 60 km sebelah selatan Jayapura. Pemeriksaan tersebut dilakukan mulai bulan Januari 1988 sampai dengan Mei 1989. DDT telah diuji pada dosis diagnostik yang telah direkomendasikan untuk jangka waktu tertentu pula. Daya tahan terhadap DDT diamati baik pada populasi nyamuk An koliensis maupun nyamuk Culex quinquefasciatus. Kira-kira 30% dari populasi nyamuk An. koliensis (sejumlah 468) ternyata tahan terhadap 4% DDT dalam kurun waktu 1 dan 2 jam paparan. Penemuan ini menunjukkan bahwa penggunaan DDT secara rutin di ARSO PIR I untuk penyemprotan di dalam mmah diperkirakan efektivitasnya terbatas, antara lain disebabkan oleh daya tahan fisiologik. Walaupun demikian, penggunaan insektisida alternatif ini akan lebih mahal dan mungkin terbukti sama tidak efektifnya karena sifat eksofilik dari jenis nyamuk tersebut. Makalah ini merupakan laporan pertama yang diperkuat dengan pengamatan yang dilakukan secara berulang-ulang mengenai kerentanan nyamuk Anopheles koliensis asal Indonesia terhadap DDT

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    DDT RESISTANCE IN ANOPHELES KOLIENSIS (DIPTERA: CULICIDAE) FROM NORTHEASTERN IRIAN JAYA, INDONESIA

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    Nyamuk Anopheles koliensis, adalah perantara (vektor) penyakit malaria yang penting di daerah pedalaman Irian Jaya, Indonesia, yang telah dievaluasi kerentanannya terhadap DDT dengan menggunakan test kit diagnostik dan kertas yang telah diresapi sesuai dengan standar WHO. Serangkaian tes telah dilakukan di ARSO PIR I, yang merupakan tempat pemukiman para transmigran yang terletak 60 km sebelah selatan Jayapura. Pemeriksaan tersebut dilakukan mulai bulan Januari 1988 sampai dengan Mei 1989. DDT telah diuji pada dosis diagnostik yang telah direkomendasikan untuk jangka waktu tertentu pula. Daya tahan terhadap DDT diamati baik pada populasi nyamuk An koliensis maupun nyamuk Culex quinquefasciatus. Kira-kira 30% dari populasi nyamuk An. koliensis (sejumlah 468) ternyata tahan terhadap 4% DDT dalam kurun waktu 1 dan 2 jam paparan. Penemuan ini menunjukkan bahwa penggunaan DDT secara rutin di ARSO PIR I untuk penyemprotan di dalam mmah diperkirakan efektivitasnya terbatas, antara lain disebabkan oleh daya tahan fisiologik. Walaupun demikian, penggunaan insektisida alternatif ini akan lebih mahal dan mungkin terbukti sama tidak efektifnya karena sifat eksofilik dari jenis nyamuk tersebut. Makalah ini merupakan laporan pertama yang diperkuat dengan pengamatan yang dilakukan secara berulang-ulang mengenai kerentanan nyamuk Anopheles koliensis asal Indonesia terhadap DDT

    Mapping the human genetic architecture of COVID-19

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    The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
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