A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Combined transcriptomic ana proteomic analysis of Pseudonaja textilis venom (Elapidae: Serpentes)

As toxinas de veneno de serpentes têm como principal função alterar a homeostase das presas para fins de alimentação ou defesa. O estudo aprofundado da composição do veneno de serpentes é importante para a produção de soros antiofídicos mais eficientes, para a descoberta de novos fármacos e na compreensão de processos biológicos, ecológicos e evolutivos. As pesquisas com toxinas têm mostrado uma versatilidade natural, refinada pela evolução, na diversificação de funções em famílias de proteínas recrutadas de suas funções endógenas, por meio de sucessivas duplicações e acumulo de mutações levando a uma evolução acelerada. A miríade de toxinas disponíveis e sua diversidade de funções ainda não foram completamente descritas. A combinação das análises em larga escala do transcriptoma de novo da glândula de veneno e do proteoma do veneno permite elaborar um perfil mais completo do toxinoma do veneno, permitindo inclusive um aumento na sensibilidade da detecção de toxinas pouco representadas e inesperadas nos venenos. O objetivo geral deste estudo foi analisar o toxinoma do veneno de uma das mais perigosas espécies australianas, a Pseudonaja textilis (Elapidae). Foi possível identificar no veneno as toxinas: fatores de coagulação de veneno do complexo protrombinase, subunidades de fosfolipases A2 (PLA2) da neurotoxina textilotoxin e PLA2 de atividade procoagulante, neurotoxinas tipo three-finger toxin (3FTx), inibidores de protease do tipo-kunitz textilinin, e pela primeira vez, uma nova variante de 3FTx, lectinas tipo C, CRiSP além de indícios de toxinas de lagarto Heloderma e outras proteínas candidatas a toxinas como calreticulin e dipeptidase 2. Metaloproteinases, pouco estudadas em Elapidae, foram clonadas e detectadas no veneno por ensaios de fracionamento e imunoreatividade. A análise do transcriptoma identificou novas isoformas e variantes de toxinas, principalmente das 3FTx e dos inibidores de serinoproteases, assim como transcritos de toxinas que não foram detectadas no veneno e que merecem mais investigações. O quadro de sintomas com acidentes em humanos é bem explicado pelas toxinas identificadas, porém, em seu habitat natural, as toxinas pouco conhecidas e até então não descritas devem ter funções importantes e específicas na predação. Identificar esta diversidade de variantes é importante para entender o modo de ação das toxinas.Snake venom toxins alter prey homeostasis for feeding or defense. In depth studies of venom composition are important for better antivenom production, for new drugs lead and discovery and for better understanding of biological, ecological and evolutionary processes. Research on toxins have shown the natures way of innovating, refined by evolution, diversifying functions of protein families recruited from their endogenous function to the venom gland by successive gene duplication and mutation accumulation, leading to an accelerated evolution. A myriad of available toxins and diversity of functions is still available for discovery. Combining high throughput techniques such as venom gland de novo transcriptomics and venom proteomics, one can assess and observe a more complete profile of the snake toxinome, additionally allowing an upscale in low represented and unexpected toxin detection. The aim of this project was to investigate the venom toxinome of one of the most dangerous Australian species, Pseudonaja textilis (Elapidae). The toxins identified in it venom was: protrombinase complex coagulation factors, neurotoxic textilotoxin phospholipase A2 (PLA2) subunits and procoagulant PLA2, neurotoxic three-finger toxins (3FTx), Kunitz-type protease inhibitor textilinin, and for the first time, a new long 3FTx, C-type lectins, CRiSPs, as well as evidences of lizard toxins from Heloderma genus and other toxin candidates calreticulin and dipeptidase 2. Metalloproteinases, little investigated in Elapidae, was cloned and detected in the venom after fractionation and immunoassay. The transcriptome revealed new toxin variants and isoforms, specially 3FTx and serine protease inhibitors, as well as transcripts from toxins not detected in the venom that deserves further investigation. Human accident symptoms are well explained by the identified toxins, however, in its natural environment, little known and undescribed toxins must have specific and important role in predation. Identifying this diversity is important to better understand toxins ways of action

Viral Metagenomics for the Identification of Emerging Infections in Clinical Samples with Inconclusive Dengue, Zika, and Chikungunya Viral Amplification

Viral metagenomics is increasingly being used for the identification of emerging and re-emerging viral pathogens in clinical samples with unknown etiology. The objective of this study was to shield light on the metavirome composition in clinical samples obtained from patients with clinical history compatible with an arboviral infection, but that presented inconclusive results when tested using RT-qPCR. The inconclusive amplification results might be an indication of the presence of an emerging arboviral agent that is inefficiently amplified by conventional PCR techniques. A total of eight serum samples with inconclusive amplification results for the routinely tested arboviruses—dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) obtained during DENV and CHIKV outbreaks registered in the state of Alagoas, Northeast Brazil between July and August 2021—were submitted to metagenomic next-generation sequencing assay using NextSeq 2000 and bioinformatic pipeline for viral discovery. The performed bioinformatic analysis revealed the presence of two arboviruses: DENV type 2 (DENV-2) and CHIKV with a high genome coverage. Further, the metavirome of those samples revealed the presence of multiple commensal viruses apparently without clinical significance. The phylogenetic analysis demonstrated that the DENV-2 genome belonged to the Asian/American genotype and clustered with other Brazilian strains. The identified CHIKV genome was taxonomically assigned as ECSA genotype, which is circulating in Brazil. Together, our results reinforce the utility of metagenomics as a valuable tool for viral identification in samples with inconclusive arboviral amplification. Viral metagenomics is one of the most potent methods for the identification of emerging arboviruses

Metagenomic insights into the plasma virome of Brazilian patients with prostate cancer

Growing evidence suggests that metavirome changes could be associated increased risk for malignant cell transformation. Considering Viruses have been proposed as factors for prostate cancer induction. The objective of this study was to examine the composition of the plasma metavirome of patients with prostate cancer. Blood samples were obtained from 49 male patients with primary prostate adenocarcinoma. Thirty blood donors were included as a control group. The obtained next-generation sequencing data were analyzed using a bioinformatic pipeline for virus metagenomics. Viral reads with higher abundance were assembled in contigs and analyzed taxonomically. Viral agents of interest were also confirmed by qPCR. Anelloviruses and the Human Pegivirus-1 (HPgV-1) were the most abundant component of plasma metavirome. Clinically important viruses like hepatitis C virus (HCV), cytomegalovirus and human adenovirus type C were also identified. In comparison, the blood donor virome was exclusively composed of torque teno virus types (TTV) types. The performed HPgV-1 and HCV phylogeny revealed that these viruses belong to commonly detected in Brazil genotypes. Our study sheds light on the plasma viral abundance in patients with prostatic cancer. The obtained viral diversity allowed us to separate the patients and controls, probably suggesting that malignant processes may influence virome composition. More complex and multiple approach investigations are necessary to examine the likely causal relationship between metavirome and its nvolvement in prostate cancer

Louis Pasteur. Papiers. V — CORRESPONDANCE. CLXXV-CLXXXVI Correspondance de Louis Pasteur. CLXXX-CLXXXVI Lettres reçues. CLXXXVI Suzor - Zévort.

Croquis. Louis PasteurLaboratoire. Expériences de Louis PasteurPasteur, Louis, de l'Académie française. PapiersPasteur, Louis, de l'Académie française. Cahier(s) de laboratoirePasteur, Louis, de l'Académie française. CroquisPasteur, Marie Laurent, Mme Louis. Portrait(s)Pasteur Vallery-Radot (Professeur et Mme Louis). Manuscrit(s) provenant d'euxSciences. Louis PasteurContient : Pasteur, Louis, de l'Académie française. Document(s) le concernant ; Terrel des Chênes, E., viticulteur. Lettre(s) ; Thiers, Adolphe, de l'Académie française, homme politique. Lettre(s) ; Thomas, Ambroise, compositeur. Lettre(s) ; Thuillier, Alexandre. Lettre(s) ; Thuillier, Françoise. Lettre(s) ; Thuillier, Louis. Lettre(s) ; Thuillier, Louis. Portrait(s) ; Thuillier, Louis. Lettre(s) reçue(s) ; Verrier, vétérinaire à Provins. Lettre(s) ; Tisserand, Louis-Eugène. Lettre(s) ; Guillemot, Gabriel, pseud. Guy Tomel. Lettre(s) ; Toussaint, Docteur Henry. Lettre(s) ; Tyndall, John, physicien. Lettre(s) ; Strachey, Général, de l'India Office. Lettre(s) ; Tyndall, John, physicien. Lettre(s) reçue(s) ; Brown, Horatio F., historien. Lettre(s) ; Simon, Docteur John. Lettre(s) ; Vaillant, Jean-Baptiste-Philibert, maréchal de France. Lettre(s) ; Vaillard, Docteur Louis, professeur au Val-de-Grâce. Lettre(s) ; Vallery-Radot, Camille. Lettre(s) ; Vallery-Radot, René, écrivain. Lettre(s) ; Roux, Docteur Émile, membre de l'Institut. Lettre(s) ; Van Tieghem, Philippe-Édouard-Léon, membre de l'Institut. Lettre(s) ; Velten, E., brasseur à Marseille. Lettre(s) ; Vercel, Jules. Lettre(s) ; Vergnette de Lamotte, Vicomte Alfred, agronome. Lettre(s) ; Viant, Joseph-Justin. Lettre(s) ; Viala, Eugène, préparateur de Pasteur. Lettre(s) ; Marès, Henri-Pierre-Louis, chimiste. Lettre(s) ; Vialla, Louis, président de la Société d'agriculture de l'Hérault. Lettre(s) ; Ministère de l'Instruction publique. Lettre(s) reçue(s) ; Vignon, Léo, chimiste. Lettre(s) ; Villemin, Docteur Jean-Antoine, de l'Académie de médecine. Lettre(s) ; Violette, Henri, commissaire à la Raffinerie impériale de salpêtre de Lille. Lettre(s) ; Viollette, Charles, physicien. Lettre(s) ; Virchow, Rudolf. Lettre(s) ; Vivier, L., chargé de cours de mathématiques au lycée de Coutances. Lettre(s) ; Vogt, Carl Christoph, naturaliste. Lettre(s) ; Vogüé, Vicomte Eugène-Melchior de, de l'Académie française. Lettre(s) ; Wallon, Henri, membre de l'Institut. Lettre(s) ; Weber, Docteur. Lettre(s) ; Woehrlin, pharmacien-chimiste à Strasbourg. Lettre(s) ; Wurtz, Docteur Adolphe, membre de l'Institut, chimiste. Lettre(s) ; Yersin, Docteur Alexandre-Émile-John. Lettre(s) ; Zévort, Désiré. Lettre(s) ; Zévort, Charles. Lettre(s) ; Zévort, Edgar, recteur d'académie. Lettre(s) ; Forthomme, Camille-Pierre-Guillaume, physicien. Lettre(s) ; Lafon, E.. Lettre(s) ; Vincent, Alexandre-Joseph-Hidulphe, membre de l'Institut. Lettre(s) ; Terquem, Alfred. Lettre(s) ; Hermann, A., professeur. Lettre(s) ; Fauré, professeur de mathématiques au collège de Melun. Lettre(s) ; Robin, P.. Lettre(s) ; Cailly, Félix. Lettre(s) ; Valatour, Martial. Lettre(s) ; Houël, Jules, mathématicien. Lettre(s) ; Leyritz, Albert-Louis, professeur. Lettre(s) ; Berger, Charles-Hippolyte, professeur. Lettre(s) ; Chevilliet. Lettre(s) ; Lamy, Claude-Auguste. Lettre(s) ; Nimier, professeur de physique. Lettre(s)Aux f. 355-386, lettres réunies par Pasteur : « Paquet de lettres d'anciens élèves de l'École relatives à ma nomination de membre de l'Académie des Sciences.

Retrospective Insights of the COVID-19 Epidemic in the Major Latin American City, São Paulo, Southeastern Brazil

São Paulo is the financial center of Brazil, with a population of over 12 million, that receives travelers from all over the world for business and tourism. It was the first city in Brazil to report a case of COVID-19 that rapidly spread across the city despite the implementation of the restriction measures. Despite many reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the city of São Paulo. Thus, in this study, we provide a retrospective overview of the COVID-19 epidemic in São Paulo City, Southeastern, Brazil, by generating a total of 9995 near-complete genome sequences from all the city’s different macro-regions (North, West, Central, East, South, and Southeast). Our analysis revealed that multiple independent introduction events of different variants (mainly Gamma, Delta, and Omicron) occurred throughout time. Additionally, our estimates of viral movement within the different macro-regions further suggested that the East and the Southeast regions were the largest contributors to the Gamma and Delta viral exchanges to other regions. Meanwhile, the North region had a higher contribution to the dispersion of the Omicron variant. Together, our results reinforce the importance of increasing SARS-CoV-2 genomic monitoring within the city and the country to track the real-time evolution of the virus and to detect earlier any eventual emergency of new variants of concern that could undermine the fight against COVID-19 in Brazil and worldwide

Retrospective Insights of the COVID-19 Epidemic in the Major Latin American City, São Paulo, Southeastern Brazil

São Paulo is the financial center of Brazil, with a population of over 12 million, that receives travelers from all over the world for business and tourism. It was the first city in Brazil to report a case of COVID-19 that rapidly spread across the city despite the implementation of the restriction measures. Despite many reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the city of São Paulo. Thus, in this study, we provide a retrospective overview of the COVID-19 epidemic in São Paulo City, Southeastern, Brazil, by generating a total of 9995 near-complete genome sequences from all the city’s different macro-regions (North, West, Central, East, South, and Southeast). Our analysis revealed that multiple independent introduction events of different variants (mainly Gamma, Delta, and Omicron) occurred throughout time. Additionally, our estimates of viral movement within the different macro-regions further suggested that the East and the Southeast regions were the largest contributors to the Gamma and Delta viral exchanges to other regions. Meanwhile, the North region had a higher contribution to the dispersion of the Omicron variant. Together, our results reinforce the importance of increasing SARS-CoV-2 genomic monitoring within the city and the country to track the real-time evolution of the virus and to detect earlier any eventual emergency of new variants of concern that could undermine the fight against COVID-19 in Brazil and worldwide