Background Integrase strand transfer inhibitor–based regimens are recommended for first-line ther... more Background Integrase strand transfer inhibitor–based regimens are recommended for first-line therapy in human immunodeficiency virus type 2 (HIV-2). Nonetheless, dolutegravir (DTG) clinical trial data are lacking. Methods We conducted a phase 2, single-arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen that included DTG in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naive adults receive DTG in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of patients who achieved a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+ T-cell count and in CD4/CD8 ratio at week 48. Results A total of 30 patients were enrolled (22 women; median age, 55 years). At baseline, 17 (56.7%) individuals were viremic (median, pVL 190 copies/mL; interquartile range [IQR], 99–445). The median CD4 count was 438 cells/μL (IQR, 335–605), and the CD4/CD8 ratio was 0.8. ...
ObjectiveTo describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly... more ObjectiveTo describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks.MethodsClinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses.ResultsIn Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (pfor–trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group prese...
Introduction: Lisbon has an intermediate incidence of tuberculosis (TB). Flexible bronchoscopy ca... more Introduction: Lisbon has an intermediate incidence of tuberculosis (TB). Flexible bronchoscopy can assist in diagnosing TB in patients with a negative smear microscopy. Earlier diagnosis by means of faster laboratory tests such as nucleic acid amplification tests (NAAT) is essential in controlling disease transmission. Objectives: Analyze the yield of bronchoscopy in diagnosing pulmonary TB and compare smear microscopy, culture and NAAT using GenoType MTBDRplus ver2.0. Methods: A retrospective analysis of TB patients hospitalized in the Infectious Disease’s ward between January 2013 and April 2016 was performed. Patients subjected to flexible bronchoscopy were selected and characterized regarding demographics and microbiological exams. Results: Fifty-eight patients were included with a mean age of 44±19 years and 71% were males. Diagnosis was confirmed by bronchoscopy in 41 (71%). Smear microscopy sensitivity was similar in bronchial wash (BW) and bronchoalveolar lavage (BAL): 39% vs 31%, p value 0.43. Culture sensitivity was also similar in BW and BAL: 70% vs 62%, p value 0.42. Culture sensitivity was superior to smear microscopy in both BW and BAL (BW: 70% vs 39%, p value Conclusion: Bronchoscopy led to diagnosis confirmation in 71% proving its importance in diagnosing pulmonary TB. NAAT sensitivity was similar to culture. NAAT is a faster diagnostic test allowing earlier treatment initiation and contributing to better control disease transmission.
About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Why dioe... more About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Why dioecious taxa are so rare is still an open question. Early work reported lower species richness in dioecious compared with nondioecious sister clades, raising the hypothesis that dioecy may be an evolutionary dead-end. This hypothesis has been recently challenged by macroevolutionary analyses that detected no or even positive effect of dioecy on diversification. However, the possible genetic consequences of dioecy at the population level, which could drive the long-term fate of dioecious lineages, have not been tested so far. Here, we used a population genomics approach in the Silene genus to look for possible effects of dioecy, especially for potential evidence of evolutionary handicaps of dioecy underlying the dead-end hypothesis. We collected individual-based RNA-seq data from several populations in 13 closely related species with different sexual systems: seven dioecious, three hermaphr...
Grapevine has a major economical and cultural importance since antiquity. A key step in domestica... more Grapevine has a major economical and cultural importance since antiquity. A key step in domestication was the transition from separate sexes (dioecy) in wild Vitis vinifera ssp. sylvestris (V. sylvestris) to hermaphroditism in cultivated Vitis vinifera ssp. vinifera. While the grapevine sex locus is known to be small, its precise boundaries, gene content and the sex-determining genes are unknown. Here we obtained a high-quality de novo reference genome for V. sylvestris and whole-genome resequencing data of a cross. Studying SNP segregation patterns, gene content and expression in wild and cultivated accessions allowed us to build a model for sex determination in grapevine. In this model, up- and down-regulation of a cytokinin regulator is sufficient to cause female sterility and reversal to hermaphroditism, respectively. This study highlights the importance of neo-functionalization of Y alleles in sex determination and provides a resource for studying genetic diversity in V. sylves...
About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Early wo... more About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Early work reported a lower species richness in dioecious compared to non-dioecious sister clades, which was taken to suggest that dioecy might be an evolutionary dead end. More recently, phylogenetic analyses using different methodologies have challenged this conclusion. Here, we used a population genomics approach to look for evidence of evolutionary handicaps of dioecy in the Silene genus at the molecular level. We obtained RNA-seq data of individuals from several populations in 13 closely related species with different breeding systems: seven dioecious, three hermaphroditic and three gynodioecious species. We show that dioecy is associated with increased genetic diversity and a higher selection efficacy both against deleterious and for beneficial mutations while controlling for differences in population size. We conclude that, in the Silene genus, dioecious species bear no sign of mutational...
Cytochromes P450 are enzymes that participate in a wide range of functions in plants, from hormon... more Cytochromes P450 are enzymes that participate in a wide range of functions in plants, from hormonal signaling and biosynthesis of structural polymers, to defense or communication with other organisms. They represent one of the largest gene/protein families in the plant kingdom. The manual annotation of cytochrome P450 genes in the genome of Vitis vinifera PN40024 revealed 579 P450 sequences, including 279 complete genes. Most of the P450 sequences in grapevine genome are organized in physical clusters, resulting from tandem or segmental duplications. Although most of these clusters are small (2 to 35, median = 3), some P450 families, such as CYP76 and CYP82, underwent multiple duplications and form large clusters of homologous sequences. Analysis of gene expression revealed highly specific expression patterns, which are often the same within the genes in large physical clusters. Some of these genes are induced upon biotic stress, which points to their role in plant defense, whereas ...
This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http:/... more This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100044).Sex chromosomes have repeatedly evolved from a pair of autosomes1. Consequently, X and Y chromosomes initially have similar gene content, but ongoing Y degeneration leads to reduced Y gene expression and eventual Y gene loss. The resulting imbalance in gene expression between Y genes and the rest of the genome is expected to reduce male fitness, especially when protein networks have components from both autosomes and sex chromosomes. A diverse set of dosage compensating mechanisms that alleviates these negative effects has been described in animals2–4. However, the early steps in the evolution of dosage compensation remain unknown and dosage compensation is poorly understood in plants5. Here we show a novel dosage compensation mechanism in the evolutionarily young XY sex determination system of the plant Silene latifolia. Genomic imprinting resul...
Expansion of the cytochrome P450 gene family is often proposed to have a critical role in the evo... more Expansion of the cytochrome P450 gene family is often proposed to have a critical role in the evolution of metabolic complexity, in particular in microorganisms, insects and plants. However, the molecular mechanisms underlying the evolution of this complexity are poorly understood. Here we describe the evolutionary history of a plant P450 retrogene, which emerged and underwent fixation in the common ancestor of Brassicales, before undergoing tandem duplication in the ancestor of Brassicaceae. Duplication leads first to gain of dual functions in one of the copies. Both sister genes are retained through subsequent speciation but eventually return to a single copy in two of three diverging lineages. In the lineage in which both copies are maintained, the ancestral functions are split between paralogs and a novel function arises in the copy under relaxed selection. Our work illustrates how retrotransposition and gene duplication can favour the emergence of novel metabolic functions.
Human infections caused by Dirofilaria repens, a cosmopolitan zoonotic parasitosis endemic in Sou... more Human infections caused by Dirofilaria repens, a cosmopolitan zoonotic parasitosis endemic in Southern and Eastern Europe and Asia still is an underdiagnosed infection due to parasite identification difficulties. Here, we report the first human case of subcutaneous dirofilariasis by D. repens diagnosed in Portugal. This was probably an imported case from India, as judged by epidemiological and clinical data. With this presentation we aim to alert clinicians for the emergence of vector-borne zoonoses associated with global warming and international travel. This case showed that differential diagnosis of D. repens in subcutaneous nodules is needed, in order to avoid further complications.
Background Integrase strand transfer inhibitor–based regimens are recommended for first-line ther... more Background Integrase strand transfer inhibitor–based regimens are recommended for first-line therapy in human immunodeficiency virus type 2 (HIV-2). Nonetheless, dolutegravir (DTG) clinical trial data are lacking. Methods We conducted a phase 2, single-arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen that included DTG in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naive adults receive DTG in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of patients who achieved a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+ T-cell count and in CD4/CD8 ratio at week 48. Results A total of 30 patients were enrolled (22 women; median age, 55 years). At baseline, 17 (56.7%) individuals were viremic (median, pVL 190 copies/mL; interquartile range [IQR], 99–445). The median CD4 count was 438 cells/μL (IQR, 335–605), and the CD4/CD8 ratio was 0.8. ...
ObjectiveTo describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly... more ObjectiveTo describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks.MethodsClinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses.ResultsIn Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (pfor–trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group prese...
Introduction: Lisbon has an intermediate incidence of tuberculosis (TB). Flexible bronchoscopy ca... more Introduction: Lisbon has an intermediate incidence of tuberculosis (TB). Flexible bronchoscopy can assist in diagnosing TB in patients with a negative smear microscopy. Earlier diagnosis by means of faster laboratory tests such as nucleic acid amplification tests (NAAT) is essential in controlling disease transmission. Objectives: Analyze the yield of bronchoscopy in diagnosing pulmonary TB and compare smear microscopy, culture and NAAT using GenoType MTBDRplus ver2.0. Methods: A retrospective analysis of TB patients hospitalized in the Infectious Disease’s ward between January 2013 and April 2016 was performed. Patients subjected to flexible bronchoscopy were selected and characterized regarding demographics and microbiological exams. Results: Fifty-eight patients were included with a mean age of 44±19 years and 71% were males. Diagnosis was confirmed by bronchoscopy in 41 (71%). Smear microscopy sensitivity was similar in bronchial wash (BW) and bronchoalveolar lavage (BAL): 39% vs 31%, p value 0.43. Culture sensitivity was also similar in BW and BAL: 70% vs 62%, p value 0.42. Culture sensitivity was superior to smear microscopy in both BW and BAL (BW: 70% vs 39%, p value Conclusion: Bronchoscopy led to diagnosis confirmation in 71% proving its importance in diagnosing pulmonary TB. NAAT sensitivity was similar to culture. NAAT is a faster diagnostic test allowing earlier treatment initiation and contributing to better control disease transmission.
About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Why dioe... more About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Why dioecious taxa are so rare is still an open question. Early work reported lower species richness in dioecious compared with nondioecious sister clades, raising the hypothesis that dioecy may be an evolutionary dead-end. This hypothesis has been recently challenged by macroevolutionary analyses that detected no or even positive effect of dioecy on diversification. However, the possible genetic consequences of dioecy at the population level, which could drive the long-term fate of dioecious lineages, have not been tested so far. Here, we used a population genomics approach in the Silene genus to look for possible effects of dioecy, especially for potential evidence of evolutionary handicaps of dioecy underlying the dead-end hypothesis. We collected individual-based RNA-seq data from several populations in 13 closely related species with different sexual systems: seven dioecious, three hermaphr...
Grapevine has a major economical and cultural importance since antiquity. A key step in domestica... more Grapevine has a major economical and cultural importance since antiquity. A key step in domestication was the transition from separate sexes (dioecy) in wild Vitis vinifera ssp. sylvestris (V. sylvestris) to hermaphroditism in cultivated Vitis vinifera ssp. vinifera. While the grapevine sex locus is known to be small, its precise boundaries, gene content and the sex-determining genes are unknown. Here we obtained a high-quality de novo reference genome for V. sylvestris and whole-genome resequencing data of a cross. Studying SNP segregation patterns, gene content and expression in wild and cultivated accessions allowed us to build a model for sex determination in grapevine. In this model, up- and down-regulation of a cytokinin regulator is sufficient to cause female sterility and reversal to hermaphroditism, respectively. This study highlights the importance of neo-functionalization of Y alleles in sex determination and provides a resource for studying genetic diversity in V. sylves...
About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Early wo... more About 15,000 angiosperm species (∼6%) have separate sexes, a phenomenon known as dioecy. Early work reported a lower species richness in dioecious compared to non-dioecious sister clades, which was taken to suggest that dioecy might be an evolutionary dead end. More recently, phylogenetic analyses using different methodologies have challenged this conclusion. Here, we used a population genomics approach to look for evidence of evolutionary handicaps of dioecy in the Silene genus at the molecular level. We obtained RNA-seq data of individuals from several populations in 13 closely related species with different breeding systems: seven dioecious, three hermaphroditic and three gynodioecious species. We show that dioecy is associated with increased genetic diversity and a higher selection efficacy both against deleterious and for beneficial mutations while controlling for differences in population size. We conclude that, in the Silene genus, dioecious species bear no sign of mutational...
Cytochromes P450 are enzymes that participate in a wide range of functions in plants, from hormon... more Cytochromes P450 are enzymes that participate in a wide range of functions in plants, from hormonal signaling and biosynthesis of structural polymers, to defense or communication with other organisms. They represent one of the largest gene/protein families in the plant kingdom. The manual annotation of cytochrome P450 genes in the genome of Vitis vinifera PN40024 revealed 579 P450 sequences, including 279 complete genes. Most of the P450 sequences in grapevine genome are organized in physical clusters, resulting from tandem or segmental duplications. Although most of these clusters are small (2 to 35, median = 3), some P450 families, such as CYP76 and CYP82, underwent multiple duplications and form large clusters of homologous sequences. Analysis of gene expression revealed highly specific expression patterns, which are often the same within the genes in large physical clusters. Some of these genes are induced upon biotic stress, which points to their role in plant defense, whereas ...
This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http:/... more This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100044).Sex chromosomes have repeatedly evolved from a pair of autosomes1. Consequently, X and Y chromosomes initially have similar gene content, but ongoing Y degeneration leads to reduced Y gene expression and eventual Y gene loss. The resulting imbalance in gene expression between Y genes and the rest of the genome is expected to reduce male fitness, especially when protein networks have components from both autosomes and sex chromosomes. A diverse set of dosage compensating mechanisms that alleviates these negative effects has been described in animals2–4. However, the early steps in the evolution of dosage compensation remain unknown and dosage compensation is poorly understood in plants5. Here we show a novel dosage compensation mechanism in the evolutionarily young XY sex determination system of the plant Silene latifolia. Genomic imprinting resul...
Expansion of the cytochrome P450 gene family is often proposed to have a critical role in the evo... more Expansion of the cytochrome P450 gene family is often proposed to have a critical role in the evolution of metabolic complexity, in particular in microorganisms, insects and plants. However, the molecular mechanisms underlying the evolution of this complexity are poorly understood. Here we describe the evolutionary history of a plant P450 retrogene, which emerged and underwent fixation in the common ancestor of Brassicales, before undergoing tandem duplication in the ancestor of Brassicaceae. Duplication leads first to gain of dual functions in one of the copies. Both sister genes are retained through subsequent speciation but eventually return to a single copy in two of three diverging lineages. In the lineage in which both copies are maintained, the ancestral functions are split between paralogs and a novel function arises in the copy under relaxed selection. Our work illustrates how retrotransposition and gene duplication can favour the emergence of novel metabolic functions.
Human infections caused by Dirofilaria repens, a cosmopolitan zoonotic parasitosis endemic in Sou... more Human infections caused by Dirofilaria repens, a cosmopolitan zoonotic parasitosis endemic in Southern and Eastern Europe and Asia still is an underdiagnosed infection due to parasite identification difficulties. Here, we report the first human case of subcutaneous dirofilariasis by D. repens diagnosed in Portugal. This was probably an imported case from India, as judged by epidemiological and clinical data. With this presentation we aim to alert clinicians for the emergence of vector-borne zoonoses associated with global warming and international travel. This case showed that differential diagnosis of D. repens in subcutaneous nodules is needed, in order to avoid further complications.
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