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1.
Mol Biol Evol ; 40(7)2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37401458

RESUMO

The recent evolutionary history of the Y chromosome in Drosophila simulans, a worldwide species of Afrotropical origin, is closely linked to that of X-linked meiotic drivers (Paris system). The spread of the Paris drivers in natural populations has elicited the selection of drive-resistant Y chromosomes. To infer the evolutionary history of the Y chromosome in relation to the Paris drive, we sequenced 21 iso-Y lines, each carrying a Y chromosome from a different location. Among them, 13 lines carry a Y chromosome that is able to counteract the effect of the drivers. Despite their very different geographical origins, all sensitive Y's are highly similar, suggesting that they share a recent common ancestor. The resistant Y chromosomes are more divergent and segregate in four distinct clusters. The phylogeny of the Y chromosome confirms that the resistant lineage predates the emergence of Paris drive. The ancestry of the resistant lineage is further supported by the examination of Y-linked sequences in the sister species of D. simulans, Drosophila sechellia and Drosophila mauritiana. We also characterized the variation in repeat content among Y chromosomes and identified multiple simple satellites associated with resistance. Altogether, the molecular polymorphism allows us to infer the demographic and evolutionary history of the Y chromosome and provides new insights on the genetic basis of resistance.


Assuntos
Drosophila simulans , Razão de Masculinidade , Animais , Drosophila simulans/genética , Cromossomo Y/genética , Evolução Biológica , Drosophila/genética
2.
Chromosome Res ; 30(2-3): 141-150, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35635636

RESUMO

Sex-ratio (SR) meiotic drivers are X-linked selfish genetic elements that promote their own transmission by preventing the production of Y-bearing sperm, which usually lowers male fertility. The spread of SR drivers in populations is expected to trigger the evolution of unlinked drive suppressors, a theoretically predicted co-evolution that has been observed in nature. Once completely suppressed, the drivers are expected either to decline if they still affect the fitness of their carriers, or to evolve randomly and possibly get fixed if the suppressors eliminate their deleterious effects. To explore this issue, we used the Paris sex-ratio system of Drosophila simulans in which drive results from the joint effect of two elements on the X chromosome: a segmental duplication and a deficient allele of the HP1D2 gene. We set up six experimental populations starting with 2/3 of X chromosomes carrying both elements (XSR) in a fully suppressing background. We let them evolve independently during almost a hundred generations under strong sexual competition, a condition known to cause the rapid disappearance of unsuppressed Paris XSR in previous experimental populations. In our study, the fate of XSR chromosomes varied among populations, from extinction to their maintenance at a frequency close to the starting one. While the reasons for these variable outcomes are still to be explored, our results show that complete suppression can prevent the demise of an otherwise deleterious XSR chromosome, turning a genetic conflict into cooperation between unlinked loci. Observations in natural populations suggest a contrasting fate of the two elements: disappearance of the duplication and maintenance of deficient HP1D2 alleles.


Assuntos
Drosophila simulans , Drosophila , Animais , Drosophila/genética , Drosophila simulans/genética , Evolução Molecular , Masculino , Meiose , Sêmen , Cromossomo X/genética
3.
Lancet Infect Dis ; 22(5): 636-648, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35090638

RESUMO

BACKGROUND: We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1-2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly in older adults, and higher than expected reactogenicity after the second vaccination were observed. In the current study, we evaluated the safety and immunogenicity of an optimised formulation of CoV2 preS dTM adjuvanted with AS03 to inform progression to phase 3 clinical trial. METHODS: This phase 2, randomised, parallel-group, dose-ranging study was done in adults (≥18 years old), including those with pre-existing medical conditions, those who were immunocompromised (except those with recent organ transplant or chemotherapy) and those with a potentially increased risk for severe COVID-19, at 20 clinical research centres in the USA and Honduras. Women who were pregnant or lactating or, for those of childbearing potential, not using an effective method of contraception or abstinence, and those who had received a COVID-19 vaccine, were excluded. Participants were randomly assigned (1:1:1) using an interactive response technology system, with stratification by age (18-59 years and ≥60 years), rapid serodiagnostic test result (positive or negative), and high-risk medical conditions (yes or no), to receive two injections (day 1 and day 22) of 5 7mu;g (low dose), 10 7mu;g (medium dose), or 15 7mu;g (high dose) CoV2 preS dTM antigen with fixed AS03 content. All participants and outcome assessors were masked to group assignment; unmasked study staff involved in vaccine preparation were not involved in safety outcome assessments. All laboratory staff performing the assays were masked to treatment. The primary safety objective was to describe the safety profile in all participants, for each candidate vaccine formulation. Safety endpoints were evaluated for all randomised participants who received at least one dose of the study vaccine (safety analysis set), and are presented here for the interim study period (up to day 43). The primary immunogenicity objective was to describe the neutralising antibody titres to the D614G variant 14 days after the second vaccination (day 36) in participants who were SARS-CoV-2 naive who received both injections, provided samples at day 1 and day 36, did not have protocol deviations, and did not receive an authorised COVID-19 vaccine before day 36. Neutralising antibodies were measured using a pseudovirus neutralisation assay and are presented here up to 14 days after the second dose. As a secondary immunogenicity objective, we assessed neutralising antibodies in non-naive participants. This trial is registered with ClinicalTrials.gov (NCT04762680) and is closed to new participants for the cohort reported here. FINDINGS: Of 722 participants enrolled and randomly assigned between Feb 24, 2021, and March 8, 2021, 721 received at least one injection (low dose=240, medium dose=239, and high dose=242). The proportion of participants reporting at least one solicited adverse reaction (injection site or systemic) in the first 7 days after any vaccination was similar between treatment groups (217 [91%] of 238 in the low-dose group, 213 [90%] of 237 in the medium-dose group, and 218 [91%] of 239 in the high-dose group); these adverse reactions were transient, were mostly mild to moderate in intensity, and occurred at a higher frequency and intensity after the second vaccination. Four participants reported immediate unsolicited adverse events; two (one each in the low-dose group and medium-dose group) were considered by the investigators to be vaccine related and two (one each in the low-dose and high-dose groups) were considered unrelated. Five participants reported seven vaccine-related medically attended adverse events (two in the low-dose group, one in the medium-dose group, and four in the high-dose group). No vaccine-related serious adverse events and no adverse events of special interest were reported. Among participants naive to SARS-CoV-2 at day 36, 158 (98%) of 162 in the low-dose group, 166 (99%) of 168 in the medium-dose group, and 163 (98%) of 166 in the high-dose group had at least a two-fold increase in neutralising antibody titres to the D614G variant from baseline. Neutralising antibody geometric mean titres (GMTs) at day 36 for participants who were naive were 2189 (95% CI 1744-2746) for the low-dose group, 2269 (1792-2873) for the medium-dose group, and 2895 (2294-3654) for the high-dose group. GMT ratios (day 36: day 1) were 107 (95% CI 85-135) in the low-dose group, 110 (87-140) in the medium-dose group, and 141 (111-179) in the high-dose group. Neutralising antibody titres in non-naive adults 21 days after one injection tended to be higher than titres after two injections in adults who were naive, with GMTs 21 days after one injection for participants who were non-naive being 3143 (95% CI 836-11 815) in the low-dose group, 2338 (593-9226) in the medium-dose group, and 7069 (1361-36 725) in the high-dose group. INTERPRETATION: Two injections of CoV2 preS dTM-AS03 showed acceptable safety and reactogenicity, and robust immunogenicity in adults who were SARS-CoV-2 naive and non-naive. These results supported progression to phase 3 evaluation of the 10 7mu;g antigen dose for primary vaccination and a 5 7mu;g antigen dose for booster vaccination. FUNDING: Sanofi Pasteur and Biomedical Advanced Research and Development Authority.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adjuvantes Imunológicos , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Imunogenicidade da Vacina , Lactação , Pessoa de Meia-Idade , Proteínas Recombinantes , SARS-CoV-2 , Vacinas Sintéticas , Adulto Jovem
4.
Virus Evol ; 7(1): veab031, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34408913

RESUMO

Drosophila melanogaster is an important model for antiviral immunity in arthropods, but very few DNA viruses have been described from the family Drosophilidae. This deficiency limits our opportunity to use natural host-pathogen combinations in experimental studies, and may bias our understanding of the Drosophila virome. Here, we report fourteen DNA viruses detected in a metagenomic analysis of 6668 pool-sequenced Drosophila, sampled from forty-seven European locations between 2014 and 2016. These include three new nudiviruses, a new and divergent entomopoxvirus, a virus related to Leptopilina boulardi filamentous virus, and a virus related to Musca domestica salivary gland hypertrophy virus. We also find an endogenous genomic copy of galbut virus, a double-stranded RNA partitivirus, segregating at very low frequency. Remarkably, we find that Drosophila Vesanto virus, a small DNA virus previously described as a bidnavirus, may be composed of up to twelve segments and thus represent a new lineage of segmented DNA viruses. Two of the DNA viruses, Drosophila Kallithea nudivirus and Drosophila Vesanto virus are relatively common, found in 2 per cent or more of wild flies. The others are rare, with many likely to be represented by a single infected fly. We find that virus prevalence in Europe reflects the prevalence seen in publicly available datasets, with Drosophila Kallithea nudivirus and Drosophila Vesanto virus the only ones commonly detectable in public data from wild-caught flies and large population cages, and the other viruses being rare or absent. These analyses suggest that DNA viruses are at lower prevalence than RNA viruses in D.melanogaster, and may be less likely to persist in laboratory cultures. Our findings go some way to redressing an earlier bias toward RNA virus studies in Drosophila, and lay the foundation needed to harness the power of Drosophila as a model system for the study of DNA viruses.

5.
J Evol Biol ; 33(10): 1345-1360, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32969551

RESUMO

Scientists are rapidly developing synthetic gene drive elements intended for release into natural populations. These are intended to control or eradicate disease vectors and pests, or to spread useful traits through wild populations for disease control or conservation purposes. However, a crucial problem for gene drives is the evolution of resistance against them, preventing their spread. Understanding the mechanisms by which populations might evolve resistance is essential for engineering effective gene drive systems. This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in general.


Assuntos
Evolução Biológica , Tecnologia de Impulso Genético , Seleção Genética
6.
Mol Biol Evol ; 37(9): 2661-2678, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32413142

RESUMO

Genetic variation is the fuel of evolution, with standing genetic variation especially important for short-term evolution and local adaptation. To date, studies of spatiotemporal patterns of genetic variation in natural populations have been challenging, as comprehensive sampling is logistically difficult, and sequencing of entire populations costly. Here, we address these issues using a collaborative approach, sequencing 48 pooled population samples from 32 locations, and perform the first continent-wide genomic analysis of genetic variation in European Drosophila melanogaster. Our analyses uncover longitudinal population structure, provide evidence for continent-wide selective sweeps, identify candidate genes for local climate adaptation, and document clines in chromosomal inversion and transposable element frequencies. We also characterize variation among populations in the composition of the fly microbiome, and identify five new DNA viruses in our samples.


Assuntos
Drosophila melanogaster/genética , Genoma de Inseto , Variação Estrutural do Genoma , Microbiota , Seleção Genética , Aclimatação/genética , Altitude , Animais , Vírus de DNA , Drosophila melanogaster/virologia , Europa (Continente) , Genoma Mitocondrial , Haplótipos , Vírus de Insetos , Masculino , Filogeografia , Polimorfismo de Nucleotídeo Único
7.
J Cell Sci ; 134(5)2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32034083

RESUMO

During transmission of malaria-causing parasites from mosquito to mammal, Plasmodium sporozoites migrate at high speed within the skin to access the bloodstream and infect the liver. This unusual gliding motility is based on retrograde flow of membrane proteins and highly dynamic actin filaments that provide short tracks for a myosin motor. Using laser tweezers and parasite mutants, we previously suggested that actin filaments form macromolecular complexes with plasma membrane-spanning adhesins to generate force during migration. Mutations in the actin-binding region of profilin, a near ubiquitous actin-binding protein, revealed that loss of actin binding also correlates with loss of force production and motility. Here, we show that different mutations in profilin, that do not affect actin binding in vitro, still generate lower force during Plasmodium sporozoite migration. Lower force generation inversely correlates with increased retrograde flow suggesting that, like in mammalian cells, the slow down of flow to generate force is the key underlying principle governing Plasmodium gliding motility.


Assuntos
Malária , Parasitos , Actinas/genética , Animais , Plasmodium berghei , Profilinas/genética , Proteínas de Protozoários/genética
8.
Proc Biol Sci ; 286(1913): 20191430, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31640520

RESUMO

Meiotic drivers are selfish genetic elements that bias their transmission into gametes, often to the detriment of the rest of the genome. The resulting intragenomic conflicts triggered by meiotic drive create evolutionary arms races and shape genome evolution. The phenomenon of meiotic drive is widespread across taxa but is particularly prominent in the Drosophila genus. Recent studies in Drosophila have provided insights into the genetic origins of drivers and their molecular mechanisms. Here, we review the current literature on mechanisms of drive with an emphasis on sperm killers in Drosophila species. In these systems, meiotic drivers often evolve from gene duplications and targets are generally linked to heterochromatin. While dense in repetitive elements and difficult to study using traditional genetic and genomic approaches, recent work in Drosophila has made progress on the heterochromatic compartment of the genome. Although we still understand little about precise drive mechanisms, studies of male drive systems are converging on common themes such as heterochromatin regulation, small RNA pathways, and nuclear transport pathways. Meiotic drive systems are therefore promising models for discovering fundamental features of gametogenesis.


Assuntos
Drosophila/fisiologia , Meiose/fisiologia , Animais , Sequências Repetitivas de Ácido Nucleico , Seleção Genética
9.
Mol Biol Evol ; 36(12): 2668-2681, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31290972

RESUMO

The recent emergence and spread of X-linked segregation distorters-called "Paris" system-in the worldwide species Drosophila simulans has elicited the selection of drive-resistant Y chromosomes. Here, we investigate the evolutionary history of 386 Y chromosomes originating from 29 population samples collected over a period of 20 years, showing a wide continuum of phenotypes when tested against the Paris distorters, from high sensitivity to complete resistance (males sire ∼95% to ∼40% female progeny). Analyzing around 13 kb of Y-linked gene sequences in a representative subset of nine Y chromosomes, we identified only three polymorphic sites resulting in three haplotypes. Remarkably, one of the haplotypes is associated with resistance. This haplotype is fixed in all samples from Sub-Saharan Africa, the region of origin of the drivers. Exceptionally, with the spread of the drivers in Egypt and Morocco, we were able to record the replacement of the sensitive lineage by the resistant haplotype in real time, within only a few years. In addition, we performed in situ hybridization, using satellite DNA probes, on a subset of 21 Y chromosomes from six locations. In contrast to the low molecular polymorphism, this revealed extensive structural variation suggestive of rapid evolution, either neutral or adaptive. Moreover, our results show that intragenomic conflicts can drive astonishingly rapid replacement of Y chromosomes and suggest that the emergence of Paris segregation distorters in East Africa occurred less than half a century ago.


Assuntos
Drosophila/genética , Evolução Molecular , Cromossomo Y , Animais , Feminino , Haplótipos , Masculino , Meiose , Filogeografia , Polimorfismo Genético , Razão de Masculinidade
10.
Heredity (Edinb) ; 122(6): 906-915, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30518968

RESUMO

Meiotic drivers are selfish genetic elements that promote their own transmission into the gametes, which results in intragenomic conflicts. In the Paris sex-ratio system of Drosophila simulans, drivers located on the X chromosome prevent the segregation of the heterochromatic Y chromosome during meiosis II, and hence the production of Y-bearing sperm. The resulting sex-ratio bias strongly impacts population dynamics and evolution. Natural selection, which tends to restore an equal sex ratio, favors the emergence of resistant Y chromosomes and autosomal suppressors. This is the case in the Paris sex-ratio system where the drivers became cryptic in most of the natural populations of D. simulans. Here, we used a quantitative trait locus (QTL) mapping approach based on the analysis of 152 highly recombinant inbred lines (RILs) to investigate the genetic determinism of autosomal suppression. The RILs were derived from an advanced intercross between two parental lines, one showing complete autosomal suppression while the other one was sensitive to drive. The confrontation of RIL autosomes with a reference XSR chromosome allowed us to identify two QTLs on chromosome 2 and three on chromosome 3, with strong epistatic interactions. Our findings highlight the multiplicity of actors involved in this intragenomic battle over the sex ratio.


Assuntos
Drosophila simulans/genética , Meiose , Locos de Características Quantitativas , Cromossomo X/genética , Animais , Mapeamento Cromossômico , Segregação de Cromossomos , Drosophila simulans/classificação , Drosophila simulans/citologia , Evolução Molecular , Feminino , Masculino , Modelos Genéticos , Filogenia , Razão de Masculinidade , Cromossomo Y
11.
PLoS Pathog ; 13(5): e1006412, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28552953

RESUMO

Profilin is an actin monomer binding protein that provides ATP-actin for incorporation into actin filaments. In contrast to higher eukaryotic cells with their large filamentous actin structures, apicomplexan parasites typically contain only short and highly dynamic microfilaments. In apicomplexans, profilin appears to be the main monomer-sequestering protein. Compared to classical profilins, apicomplexan profilins contain an additional arm-like ß-hairpin motif, which we show here to be critically involved in actin binding. Through comparative analysis using two profilin mutants, we reveal this motif to be implicated in gliding motility of Plasmodium berghei sporozoites, the rapidly migrating forms of a rodent malaria parasite transmitted by mosquitoes. Force measurements on migrating sporozoites and molecular dynamics simulations indicate that the interaction between actin and profilin fine-tunes gliding motility. Our data suggest that evolutionary pressure to achieve efficient high-speed gliding has resulted in a unique profilin-actin interface in these parasites.


Assuntos
Actinas/metabolismo , Malária/parasitologia , Plasmodium berghei/citologia , Plasmodium berghei/metabolismo , Profilinas/metabolismo , Proteínas de Protozoários/metabolismo , Actinas/genética , Animais , Movimento Celular , Feminino , Humanos , Camundongos Endogâmicos C57BL , Plasmodium berghei/genética , Plasmodium berghei/crescimento & desenvolvimento , Profilinas/genética , Ligação Proteica , Proteínas de Protozoários/genética , Esporozoítos/citologia , Esporozoítos/crescimento & desenvolvimento , Esporozoítos/metabolismo
12.
Elife ; 62017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28525314

RESUMO

Gliding motility allows malaria parasites to migrate and invade tissues and cells in different hosts. It requires parasite surface proteins to provide attachment to host cells and extracellular matrices. Here, we identify the Plasmodium protein LIMP (the name refers to a gliding phenotype in the sporozoite arising from epitope tagging of the endogenous protein) as a key regulator for adhesion during gliding motility in the rodent malaria model P. berghei. Transcribed in gametocytes, LIMP is translated in the ookinete from maternal mRNA, and later in the sporozoite. The absence of LIMP reduces initial mosquito infection by 50%, impedes salivary gland invasion 10-fold, and causes a complete absence of liver invasion as mutants fail to attach to host cells. GFP tagging of LIMP caused a limping defect during movement with reduced speed and transient curvature changes of the parasite. LIMP is an essential motility and invasion factor necessary for malaria transmission.


Assuntos
Culicidae/parasitologia , Locomoção , Plasmodium berghei/fisiologia , Proteínas de Protozoários/metabolismo , Esporozoítos/fisiologia , Fatores de Virulência/metabolismo , Animais , Modelos Animais de Doenças , Fígado/parasitologia , Malária/parasitologia , Proteínas de Membrana/metabolismo , Camundongos
13.
J Child Adolesc Trauma ; 10(1): 51-61, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29308104

RESUMO

Child sexual abuse (CSA) is identified as a significant risk factor for later victimization in the context of adult intimate relationships, but less is known about the risk associated with CSA in early romantic relationships. This paper aims to document the association between CSA and teen dating victimization in a large representative sample of Quebec high-school students. As part of the Youths' Romantic Relationships Project, 8,194 teens completed measures on CSA and psychological, physical and sexual dating violence. After controlling for other interpersonal traumas, results show that CSA contributed to all three forms of dating victimization among both boys and girls. The heightened risk of revictimization appears to be stronger for male victims of CSA. Intervention and prevention efforts are clearly needed to reduce the vulnerability of male and female victims of sexual abuse who are entering the crucial phase of adolescence and first romantic relationships.

14.
Proc Natl Acad Sci U S A ; 113(15): 4110-5, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-26979956

RESUMO

Sex chromosome meiotic drive, the non-Mendelian transmission of sex chromosomes, is the expression of an intragenomic conflict that can have extreme evolutionary consequences. However, the molecular bases of such conflicts remain poorly understood. Here, we show that a young and rapidly evolving X-linked heterochromatin protein 1 (HP1) gene, HP1D2, plays a key role in the classical Paris sex-ratio (SR) meiotic drive occurring in Drosophila simulans Driver HP1D2 alleles prevent the segregation of the Y chromatids during meiosis II, causing female-biased sex ratio in progeny. HP1D2 accumulates on the heterochromatic Y chromosome in male germ cells, strongly suggesting that it controls the segregation of sister chromatids through heterochromatin modification. We show that Paris SR drive is a consequence of dysfunctional HP1D2 alleles that fail to prepare the Y chromosome for meiosis, thus providing evidence that the rapid evolution of genes controlling the heterochromatin structure can be a significant source of intragenomic conflicts.


Assuntos
Evolução Molecular , Heterocromatina/metabolismo , Meiose/genética , Cromossomo Y , Animais , Drosophila simulans/classificação , Drosophila simulans/genética , Filogenia
15.
Trends Ecol Evol ; 31(4): 315-326, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26920473

RESUMO

Meiotic drivers are genetic variants that selfishly manipulate the production of gametes to increase their own rate of transmission, often to the detriment of the rest of the genome and the individual that carries them. This genomic conflict potentially occurs whenever a diploid organism produces a haploid stage, and can have profound evolutionary impacts on gametogenesis, fertility, individual behaviour, mating system, population survival, and reproductive isolation. Multiple research teams are developing artificial drive systems for pest control, utilising the transmission advantage of drive to alter or exterminate target species. Here, we review current knowledge of how natural drive systems function, how drivers spread through natural populations, and the factors that limit their invasion.


Assuntos
Evolução Biológica , Fenômenos Ecológicos e Ambientais/genética , Meiose/genética , Animais , Feminino , Gametogênese/genética , Masculino , Reprodução/genética , Seleção Genética
16.
Mol Biol Cell ; 27(6): 941-53, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26792835

RESUMO

Angiogenesis involves the coordinated growth and migration of endothelial cells (ECs) toward a proangiogenic signal. The Wnt planar cell polarity (PCP) pathway, through the recruitment of Dishevelled (Dvl) and Dvl-associated activator of morphogenesis (Daam1), has been proposed to regulate cell actin cytoskeleton and microtubule (MT) reorganization for oriented cell migration. Here we report that Kif26b--a kinesin--and Daam1 cooperatively regulate initiation of EC sprouting and directional migration via MT reorganization. First, we find that Kif26b is recruited within the Dvl3/Daam1 complex. Using a three-dimensional in vitro angiogenesis assay, we show that Kif26b and Daam1 depletion impairs tip cell polarization and destabilizes extended vascular processes. Kif26b depletion specifically alters EC directional migration and mislocalized MT organizing center (MTOC)/Golgi and myosin IIB cell rear enrichment. Therefore the cell fails to establish a proper front-rear polarity. Of interest, Kif26b ectopic expression rescues the siDaam1 polarization defect phenotype. Finally, we show that Kif26b functions in MT stabilization, which is indispensable for asymmetrical cell structure reorganization. These data demonstrate that Kif26b, together with Dvl3/Daam1, initiates cell polarity through the control of PCP signaling pathway-dependent activation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Polaridade Celular , Proteínas Desgrenhadas/metabolismo , Células Endoteliais/metabolismo , Cinesinas/metabolismo , Via de Sinalização Wnt , Animais , Movimento Celular , Células Endoteliais/fisiologia , Humanos , Camundongos , Proteínas dos Microfilamentos , Centro Organizador dos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Neovascularização Fisiológica , Proteínas rho de Ligação ao GTP
17.
ACS Nano ; 10(2): 2091-102, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26792112

RESUMO

Migration of malaria parasites is powered by a myosin motor that moves actin filaments, which in turn link to adhesive proteins spanning the plasma membrane. The retrograde flow of these adhesins appears to be coupled to forward locomotion. However, the contact dynamics between the parasite and the substrate as well as the generation of forces are complex and their relation to retrograde flow is unclear. Using optical tweezers we found retrograde flow rates up to 15 µm/s contrasting with parasite average speeds of 1-2 µm/s. We found that a surface protein, TLP, functions in reducing retrograde flow for the buildup of adhesive force and that actin dynamics appear optimized for the generation of force but not for maximizing the speed of retrograde flow. These data uncover that TLP acts by modulating actin dynamics or actin filament organization and couples retrograde flow to force production in malaria parasites.


Assuntos
Movimento Celular/fisiologia , Malária/parasitologia , Plasmodium berghei/fisiologia , Proteínas de Protozoários/química , Proteínas de Protozoários/metabolismo , Esporozoítos/fisiologia , Actinas/química , Actinas/metabolismo , Animais , Fenômenos Biomecânicos , Camundongos , Plasmodium berghei/química , Esporozoítos/química
18.
Cien Saude Colet ; 20(11): 3417-26, 2015 Nov.
Artigo em Inglês, Português | MEDLINE | ID: mdl-26602719

RESUMO

Analyzing violent events in the amorous trajectory of young people mobilizes researchers worldwide. The scope of this study is to perform the cross-cultural adaptation and content validation of the Canadian Parcours Amoureux des Jeunes (PAJ) inventory in the Brazilian context. It is a methodological study with the following steps: (a) translation and back-translation; (b) committee of experts (10) for analysis of equivalence, clarity and matching percentages; (c) calculation of the Content Validity Index / CVI. This analysis generated Pilot version III (d) submitted to a pre-test group of 36 adolescents aged 14 to 24 of both sexes to obtain cultural, conceptual, semantic and idiomatic equivalence. The PAJ showed adequate content validity (CVI 0.97). In section 1 (sociodemographic aspects of youths and families inherent to the Canadian context), the questions were appropriate to the Brazilian context shown by the low value of the CVI. Cross-cultural adaptation and content validation processes showed that the PAJ had adequate clarity and equivalence properties. This step makes it viable to conduct psychometric analysis to assess the replicability and reliability of the instrument to be applied in the Brazilian context.


Assuntos
Comparação Transcultural , Relações Interpessoais , Violência , Adolescente , Adulto , Brasil , Canadá , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
19.
Ciênc. Saúde Colet. (Impr.) ; 20(11): 3417-3426, Nov. 2015. graf
Artigo em Português | LILACS | ID: lil-766409

RESUMO

Analisar eventos violentos no percurso amoroso de jovens mobiliza estudiosos em nível mundial. O objetivo deste estudo é realizar a adaptação transcultural e validação de conteúdo do inventário PAJ Parcours Amourex des Jeunes, do Canadá, para o contexto brasileiro. Estudo metodológico envolvendo etapas: (a) Tradução e Retrotradução; (b) Comitê de Especialistas (10) – análise da equivalência, clareza e porcentagens de concordância; (c) Cálculo do Índice de Validade de Conteúdo/IVC. Esta análise originou a versão Piloto III: (d) Submissão ao Pré-teste com grupo de 36 jovens, de 14 a 24 anos, ambos os sexos, visando obter equivalências cultural, conceitual, semântica, idiomática. O PAJ apresentou adequada validade de conteúdo (IVC 0,97). Na seção 1 (aspectos sociodemográficos de jovens e famílias, inerentes ao contexto canadense), as questões foram adequadas ao contexto brasileiro pelo baixo valor do IVC. Os processos de adaptação transcultural e validação de conteúdo apontaram que o PAJ apresentou adequação nas propriedades de clareza e equivalência. Esta etapa viabiliza as análises psicométricas visando à reprodutibilidade e confiabilidade do instrumento a ser aplicado no contexto brasileiro.


Analyzing violent events in the amorous trajectory of young people mobilizes researchers worldwide. The scope of this study is to perform the cross-cultural adaptation and content validation of the Canadian Parcours Amoureux des Jeunes (PAJ) inventory in the Brazilian context. It is a methodological study with the following steps: (a) translation and back-translation; (b) committee of experts (10) for analysis of equivalence, clarity and matching percentages; (c) calculation of the Content Validity Index / CVI. This analysis generated Pilot version III (d) submitted to a pre-test group of 36 adolescents aged 14 to 24 of both sexes to obtain cultural, conceptual, semantic and idiomatic equivalence. The PAJ showed adequate content validity (CVI 0.97). In section 1 (sociodemographic aspects of youths and families inherent to the Canadian context), the questions were appropriate to the Brazilian context shown by the low value of the CVI. Cross-cultural adaptation and content validation processes showed that the PAJ had adequate clarity and equivalence properties. This step makes it viable to conduct psychometric analysis to assess the replicability and reliability of the instrument to be applied in the Brazilian context.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Violência , Comparação Transcultural , Relações Interpessoais , Brasil , Canadá , Inquéritos e Questionários , Reprodutibilidade dos Testes
20.
Arch Sex Behav ; 44(1): 223-31, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25119389

RESUMO

The assessment of intimate partner sexual violence (IPSV) has garnered increased attention in recent years. However, uncertainty about which measure best captures experiences of IPSV remains. The present study focused on the direct comparison of two widely used measures of IPSV: the revised Sexual Experiences Survey (SES) and the revised Conflict Tactics Scales (CTS2). A secondary aim of the study was to extend the scope of IPSV acts by evaluating the presence of pornographic acts and experiences of forced sexual relations with other individuals. The current sample consisted of 138 battered women using the services of shelters. Results indicated that 79.7 % of women reported at least one incident of IPSV on either the CTS2 or the SES. The concordance rate between both measures was 76.8 %, with the highest concordance being for severe sexual violence. The Sexual Violence scale of the CTS2, which is more concise than the SES, identified 16.7 % more cases of IPSV. In addition, 26.1 % of women reported at least one incident involving pornography and 9.4 % had been forced to engage in sexual activities with other individuals. Women who reported experiences associated with pornography were 12-20 times more likely to be victims of severe sexual violence on the two measures. Such findings confirm the high prevalence of sexual violence among this population and indicate how rates can vary depending on the measures used. This study also underscores the relevance of investigating diverse types of violent acts to better understand how IPSV manifests itself.


Assuntos
Mulheres Maltratadas/estatística & dados numéricos , Delitos Sexuais/estatística & dados numéricos , Adulto , Idoso , Coerção , Estudos de Coortes , Coleta de Dados , Literatura Erótica , Feminino , Humanos , Pessoa de Meia-Idade , Quebeque/epidemiologia , Adulto Jovem
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