Механизмы образования мишенных инсерций при синтезе молекулы ДНК, содержащей цис-син циклобутановые цитозиновые димеры

В рамках развиваемой полимеразно-таутомерной модели ультрафиолетового мутагенеза предлагается модель механизма образования мишенных инсерций, вызванных цис-син циклобутановыми цитозиновыми димерами. Инсерции — это мутации сдвига рамки чтения, когда встраивается одно или несколько оснований ДНК. Структурный анализ встраивания оснований показал, что напротив двух редких таутомерных форм цитозина невозможно встроить ни одно из канонических оснований так, чтобы между ними и матричными основаниями образовались водородные связи. Поэтому при синтезе молекулы ДНК, содержащей цис-син циклобутановые цитозиновые димеры, содержащие молекулы цитозина в таких редких таутомерных формах, специализированные или модифицированные ДНК-полимеразы напротив этих цис-син циклобутановых цитозиновых димеров будут оставлять бреши в один нуклеотид. На участках ДНК с однородным нуклеотидным составом, в соответствии с моделью Стрейзингера, конец нити ДНК может сползти, соединиться с помощью водородных связей так, что образуется петля. В результате дочерняя нить удлиняется, появляется мишенная мутация сдвига рамки чтения — мишенная инсерция.У рамках розроблюваної полiмеразно-таутомерної моделi ультрафiолетового мутагенезу, запропоновано модель механiзму формування мiшенних iнсерцiй, що викликанi цис-син циклобутановими цитозиновими димерами. Iнсерцiї — це мутацiї зсуву рамки читання, коли вбудовується одна або декiлька основ ДНК. Структурний аналiз вбудовування основ показав, що навпроти двох рiдких таутомерних станiв цитозину неможливо вбудувати жодну з канонiчних основ так, щоб мiж ними та матричними основами сформувались водневi зв’язки. Тому при синтезi молекули ДНК, що мiстить цис-син циклобутановi цитозиновi димери, що мають молекули цитозину в таких рiдких таутомерних формах, спецiалiзованi або модифiкованi ДНК-полiмерази навпроти цих цис-син циклобутанових цитозинових димерiв будуть залишати проломи в один нуклеотид. На дiлянках ДНК з однорiдним нуклеотидним складом, вiдповiдно до моделi Стрейзингера, кiнець нитки ДНК може сповзти, з’єднатися за допомогою водневих зв’язкiв так, що утвориться петля. У результатi подовжується дочiрня нитка, з’являється мiшенна мутацiя зсуву рамки читання — мiшенна iнсерцiя.A polymerase — tautomer model of ultraviolet mutagenesis is developed. The mechanism of formation of targeted insertions that is caused by cis-syn cyclobutane cytosine dimers is proposed. Insertions are frameshift mutations, when one or several DNA bases are inserted. Structural analysis has shown that, opposite two rare tautomeric forms of cytosine, it is impossible to insert any canonical DNA bases with template bases with the formation of hydrogen bonds. Therefore, under the synthesis of DNA containing cis-syn cyclobutane cytosine dimers with cytosine molecules in such rare tautomeric forms, specialized or modified DNA polymerases will leave one nucleotide gaps opposite these cis-syn cyclobutane cytosine dimers. On DNA sites with homogeneous nucleotide composition, the end of a DNA strand may slip and join with hydrogen bonds so that a loop is formed by the Streisinger model. As a result, the daughter strand is elongated, and the targeted insertion is formed

Les problèmes de conservation du manioc en cossettes au Congo

Une liste est fournie des insectes infestant les cossettes de manioc séchées au Congo. Au total, 12 espèces de coléoptères nuisibles ont été identifiées ; la plus nuisible est #Araecerus fasciculatus$. (Résumé d'auteur

Propriétés insecticides de Chenopodium ambrosoides et Tephrosia vogelii vers la bruche de l'arachide Caryedon serratus

L'efficacité de poudres de #Tephrosia vogelii (une source connue de roténone) et de cinq autres plantes utilisées traditionnellement au Congo pour la protection des stocks contre les insectes, a été évaluée. A la dose de 1 pour 40, #Chenopodium ambrosioides et #Tephrosia vogelii affectent la survie des adultes de #Caryedon serratus : 90,0 et 98,8 %, respectivement, meurent au bout de 13 jours. Le nombre d'oeufs pondus est très faible ou nul. Les autres plantes n'ont aucun effet ou un effet mineur sur les différents stades de l'insecte. (Résumé d'auteur

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Insecticidal properties of six plant materials against Caryedon serratus (Ol.) (Coleoptera : Bruchidae)

L'efficacité de poudres de #Tephrosia vogelii (une source connue de roténone) et de cinq autres plantes utilisées traditionnellement au Congo a été évaluée. A la dose de 1:40, #Chenopodium ambroisioides et #T. vogelii affectent la survie des adultes de #C. serratus, 90,0 et 98,8 % d'entre eux (respectivement) meurent au bout de 13 jours. Le nombre d'oeufs pondus est très faible ou nul. Les autres plantes n'ont aucun effet ou un effet mineur sur les différents stades de l'insecte. (Résumé d'auteur

« Effet de case » et « contamination familiale » dans la maladie du sommeil : essai d’interprétation du phénomène

Cet article présente différentes hypothèses possibles pour expliquer le phénomène connu sous le nom « d’effet de case » ou « contamination familiale ». Il s’agit : 1) de la transmission mécanique par des arthropodes hématophages contaminant des individus vivant ensemble. 2) d’une série de repas interrompus pris sur plusieurs personnes par une glossine cycliquement infectante. 3) d’un facteur biologique familial. Ces différentes hypothèses sont discutées et présentées comme une introduction à une étude de la distribution spatiale et familiale des trypanosomés dans trois foyers congolais. Celle-ci montre une répartition aléatoire des malades dans les quartiers des villages, mais leur regroupement au niveau des habitations et des familles. Ce phénomène s’expliquerait par l’activité communautaire des membres des cellules familiales (déplacements, travaux aux champs, baignades) associée à un phénomène amplificateur, le plus probable étant les repas interrompus d’une glossine cycliquement infectante. Dans certains cas d’autres possibilités, telles que la transmission mécanique par glossines ou Aedes, ou encore un facteur biologique familial, peuvent être envisagées. Ce phénomène, qui constitue l’une des caractéristiques épidémiologiques les plus remarquables la maladie du sommeil, a comme conséquence, la surveillance étroite de l’entourage des malades

Therapeutic efficacy of sulfadoxine-pyrimethamine and the prevalence of molecular markers of resistance in under 5-year olds in Brazzaville, Congo

OBJECTIVE To test the efficacy of sulfadoxine-pyremethamine (SP) monotherapy and establish the prevalence of mutations in dhfr and dhps in Brazzaville, Congo. METHOD We recruited 97 patients aged 6-59 months with uncomplicated malaria who attended Tenrikyo public health Centre. Eighty-three were followed until day 28. SP efficacy was determined by the WHO 28-day test and analysis of mutations in the Plasmodium falciparum dihydrofolate reductase (pfdhfr) and clihydropteroate synthase (pfhbps) genes. RESULTs There were seven (8.4%) early treatment failures, 23 late treatment failures (27.7%), nine (10.8%) late parasitological failures and 44 (53%) adequate clinical and parasitological responses (ACPR). After polymerase chain reaction (PCR) analysis of 64 available samples, the corrected results there were 44 (68.8%) ACPR and 19 recrudescent cases (31.2%). Approximately, 97.5% of samples bore the Asn51lle mutation, 66.2% the Cys59Arg mutation and 98.8% the Ser108Asn mutation. Mutations of dhps at positions 437 (Ala-Gly) and 436 (Ser-Ala) were found in 85% and 12.5% of samples. Quadruple mutations (pfdhfr triple mutations in codons 51, 59 and 108+ pfdhps mutation in 437) were found in 42 samples (52.5%) and associated with treatment failures. CONCLUSION This high level of treatment failures and mutations in both genes calls for the urgent application of the new policy for malaria treatment to delay the spread of SP resistance