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The ATRX ATP-dependent chromatin remodelling/helicase protein associates with the DAXX histone chaperone to deposit histone H3.3 over repetitive DNA regions. Because ATRX-protein interactions impart functions, such as histone deposition, we used proximity-dependent biotinylation (BioID) to identify proximal associations for ATRX. The proteomic screen captured known interactors, such as DAXX, NBS1, and PML, but also identified a range of new associating proteins. To gauge the scope of their roles, we examined three novel ATRX-associating proteins that likely differed in function, and for which little data were available. We found CCDC71 to associate with ATRX, but also HP1 and NAP1, suggesting a role in chromatin maintenance. Contrastingly, FAM207A associated with proteins involved in ribosome biosynthesis and localized to the nucleolus. ATRX proximal associations with the SLF2 DNA damage response factor help inhibit telomere exchanges. We further screened for the proteomic changes at telomeres when ATRX, SLF2, or both proteins were deleted. The loss caused important changes in the abundance of chromatin remodelling, DNA replication, and DNA repair factors at telomeres. Interestingly, several of these have previously been implicated in alternative lengthening of telomeres. Altogether, this study expands the repertoire of ATRX-associating proteins and functions.
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Proteínas Correpressoras/genética , Proteínas de Ligação a DNA/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Proteína Nuclear Ligada ao X/genética , Biotinilação/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular , Cromatina/genética , Homólogo 5 da Proteína Cromobox/genética , Dano ao DNA/genética , Reparo do DNA/genética , Chaperonas de Histonas/genética , Histonas/genética , Humanos , Chaperonas Moleculares/genética , Proteína da Leucemia Promielocítica/genética , Telômero/genética , tRNA MetiltransferasesRESUMO
Microplastics are contaminants of emerging concern, not least due to their global presence in marine surface waters. Unsurprisingly, microplastics have been reported in salts harvested from numerous locations. We extracted microplastics from 13 European sea salts through 30% H2O2 digestion and filtration over 5-µm filters. Filters were visually inspected at magnifications to x100. A subsample of potential microplastics was subjected to Raman spectroscopy. Particle mass was estimated, and human dose exposure calculated. After blank corrections, median concentrations were 466 ± 152 microplastics kg-1 ranging from 74 to 1155 items kg-1. Traditionally harvested salts contained fewer microplastics than most industrially harvested ones (t-test, p < 0.01). Approximately 14 µg of microplastics (< 12 particles) may be absorbed by the human body annually, of which a quarter may derive from a consumer choosing sea salt. We reviewed existing studies, showing that targeting different particle sizes and incomplete filtrations hinder interstudy comparison, indicating the importance of method harmonisation for future studies. Excess salt consumption is detrimental to human health; the hazardousness of ingesting microplastics on the other hand has yet to be shown. A portion of microplastics may enter sea salts through production processes rather than source materials.
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Microplásticos , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Peróxido de Hidrogênio , Plásticos , Sais , Poluentes Químicos da Água/análiseRESUMO
Functional trait-based approaches are increasingly adopted to understand and project ecological responses to environmental change; however, most assume trait expression is constant between conspecifics irrespective of context. Using two species of benthic invertebrate (brittlestars Amphiura filiformis and Amphiura chiajei), we demonstrate that trait expression at individual and community levels differs with biotic and abiotic context. We use PERMANOVA to test the effect of species identity, density and local environmental history on individual (righting and burrowing) and community (particle reworking and burrow ventilation) trait expression, as well as associated effects on ecosystem functioning (sediment nutrient release). Trait expression differs with context, with repercussions for the faunal mediation of ecosystem processes; we find increased rates of righting and burial behaviour and greater particle reworking with increasing density that are reflected in nutrient generation. However, the magnitude of effects differed within and between species, arising from site-specific environmental and morphological differences. Our results indicate that traits and processes influencing change in ecosystem functioning are products of both prevailing and historic conditions that cannot be constrained within typologies. Trait-based study must incorporate context-dependent variation, including intraspecific differences from individual to ecosystem scales, to avoid jeopardizing projections of ecosystem functioning and service delivery.
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Organismos Aquáticos/fisiologia , Invertebrados/fisiologia , Animais , Comportamento Animal , Biodiversidade , Equinodermos/fisiologia , Ecossistema , FenótipoRESUMO
Arctic marine ecosystems are undergoing rapid correction in response to multiple expressions of climate change, but the consequences of altered biodiversity for the sequestration, transformation and storage of nutrients are poorly constrained. Here, we determine the bioturbation activity of sediment-dwelling invertebrate communities over two consecutive summers that contrasted in sea-ice extent along a transect intersecting the polar front. We find a clear separation in community composition at the polar front that marks a transition in the type and amount of bioturbation activity, and associated nutrient concentrations, sufficient to distinguish a southern high from a northern low. While patterns in community structure reflect proximity to arctic versus boreal conditions, our observations strongly suggest that faunal activity is moderated by seasonal variations in sea ice extent that influence food supply to the benthos. Our observations help visualize how a climate-driven reorganization of the Barents Sea benthic ecosystem may be expressed, and emphasize the rapidity with which an entire region could experience a functional transformation. As strong benthic-pelagic coupling is typical across most parts of the Arctic shelf, the response of these ecosystems to a changing climate will have important ramifications for ecosystem functioning and the trophic structure of the entire food web. This article is part of the theme issue 'The changing Arctic Ocean: consequences for biological communities, biogeochemical processes and ecosystem functioning'.
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Mudança Climática , Ecossistema , Invertebrados/crescimento & desenvolvimento , Animais , Organismos Aquáticos/classificação , Organismos Aquáticos/crescimento & desenvolvimento , Organismos Aquáticos/isolamento & purificação , Regiões Árticas , Biodiversidade , Cadeia Alimentar , Sedimentos Geológicos/química , Camada de Gelo , Invertebrados/classificação , Noruega , Oceanos e Mares , Estações do AnoRESUMO
BACKGROUND: In eukaryotic genomes, deletion or amplification rates have been estimated to be a thousand more frequent than single nucleotide variation. In Plasmodium falciparum, relatively few transcription factors have been identified, and the regulation of transcription is seemingly largely influenced by gene amplification events. Thus copy number variation (CNV) is a major mechanism enabling parasite genomes to adapt to new environmental changes. METHODS: Currently, the detection of CNVs is based on quantitative PCR (qPCR), which is significantly limited by the relatively small number of genes that can be analysed at any one time. Technological advances that facilitate whole-genome sequencing, such as next generation sequencing (NGS) enable deeper analyses of the genomic variation to be performed. Because the characteristics of Plasmodium CNVs need special consideration in algorithms and strategies for which classical CNV detection programs are not suited a dedicated algorithm to detect CNVs across the entire exome of P. falciparum was developed. This algorithm is based on a custom read depth strategy through NGS data and called PlasmoCNVScan. RESULTS: The analysis of CNV identification on three genes known to have different levels of amplification and which are located either in the nuclear, apicoplast or mitochondrial genomes is presented. The results are correlated with the qPCR experiments, usually used for identification of locus specific amplification/deletion. CONCLUSIONS: This tool will facilitate the study of P. falciparum genomic adaptation in response to ecological changes: drug pressure, decreased transmission, reduction of the parasite population size (transition to pre-elimination endemic area).
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Variações do Número de Cópias de DNA , Genoma de Protozoário , Plasmodium/genética , Proteínas de Protozoários/genética , Camboja , Citocromos b/genética , Genômica , Haploidia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Deciphering the genetic architecture of complex traits is still a major challenge for human genetics. In most cases, genome-wide association studies have only partially explained the heritability of traits and diseases. Epistasis, one potentially important cause of this missing heritability, is difficult to explore at the genome-wide level. Here, we develop and assess a tool based on interactive odds ratios (IOR), Fast Odds Ratio-based sCan for Epistasis (FORCE), as a novel approach for exhaustive genome-wide epistasis search. IOR is the ratio between the multiplicative term of the odds ratio (OR) of having each variant over the OR of having both of them. By definition, an IOR that significantly deviates from 1 suggests the occurrence of an interaction (epistasis). As the IOR is fast to calculate, we used the IOR to rank and select pairs of interacting polymorphisms for P value estimation, which is more time consuming. RESULTS: FORCE displayed power and accuracy similar to existing parametric and non-parametric methods, and is fast enough to complete a filter-free genome-wide epistasis search in a few days on a standard computer. Analysis of psoriasis data uncovered novel epistatic interactions in the HLA region, corroborating the known major and complex role of the HLA region in psoriasis susceptibility. CONCLUSIONS: Our systematic study revealed the ability of FORCE to uncover novel interactions, highlighted the importance of exhaustiveness, as well as its specificity for certain types of interactions that were not detected by existing approaches. We therefore believe that FORCE is a valuable new tool for decoding the genetic basis of complex diseases.
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Epistasia Genética , Estudo de Associação Genômica Ampla/métodos , Antígenos de Histocompatibilidade/genética , Psoríase/genética , Software , Cromossomos Humanos Par 6 , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Substantial research exists on predation and its ecology. Most research has focused on durophagous fishes, brachyuran crabs, and lobsters. Data are lacking, however, on soft-bodied predators like anemones, and their contribution to overall levels of predation remains largely unevaluated. Here, we compared predation rates of the durophagous predator, the crab C. maenas and the soft-bodied predator, the anemone Actinia equina on 15 intertidal shores around Anglesey, north Wales, UK. We employed a novel approach to assess predation based on measuring faecal output from recently collected individuals and converting it to food consumed using absorption efficiencies (AEs) measured using potential prey species inhabiting the same shores. Anemone mean abundance was 8.21 (± 0.27, s.e.) individuals.m-2, whereas for C. maenas it was 0.23 (± 0.02, s.e.) individuals.m-2. AEs when fed mussel tissue, a polychaete worm, or a shrimp were 92.8-94.0% in C. maenas and 40.5-95.8% in A. equina. This difference in values reflected the different feeding modes of the two predators. Unexpectedly, A. equina consumed 3.5-7 times more prey than C. maenas. The consumption of larger amounts of prey by an anemone than the dominant durophagous predator has important consequences for calculating energy flows in food webs, understanding predation controls in assemblages, and potentially for wider predation trends.
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Lithodid crabs (and other skeleton-crushing predators) may have been excluded from cold Antarctic continental shelf waters for more than 14 Myr. The west Antarctic Peninsula shelf is warming rapidly and has been hypothesized to be soon invaded by lithodids. A remotely operated vehicle survey in Palmer Deep, a basin 120 km onto the Antarctic shelf, revealed a large, reproductive population of lithodids, providing the first evidence that king crabs have crossed the Antarctic shelf. DNA sequencing and morphology indicate the lithodid is Neolithodes yaldwyni Ahyong & Dawson, previously reported only from Ross Sea waters. We estimate a N. yaldwyni population density of 10 600 km(-2) and a population size of 1.55 × 10(6) in Palmer Deep, a density similar to lithodid populations of commercial interest around Alaska and South Georgia. The lithodid occurred at depths of more than 850 m and temperatures of more than 1.4°C in Palmer Deep, and was not found in extensive surveys of the colder shelf at depths of 430-725 m. Where N. yaldwyni occurred, crab traces were abundant, megafaunal diversity reduced and echinoderms absent, suggesting that the crabs have major ecological impacts. Antarctic Peninsula shelf waters are warming at approximately 0.01°C yr(-1); if N. yaldwyni is currently limited by cold temperatures, it could spread up onto the shelf (400-600 m depths) within 1-2 decades. The Palmer Deep N. yaldwyni population provides an important model for the potential invasive impacts of crushing predators on vulnerable Antarctic shelf ecosystems.
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Anomuros/fisiologia , Espécies Introduzidas , Animais , Regiões Antárticas , Biodiversidade , Mudança Climática , Densidade Demográfica , Dinâmica PopulacionalRESUMO
Unprecedented and dramatic transformations are occurring in the Arctic in response to climate change, but academic, public, and political discourse has disproportionately focussed on the most visible and direct aspects of change, including sea ice melt, permafrost thaw, the fate of charismatic megafauna, and the expansion of fisheries. Such narratives disregard the importance of less visible and indirect processes and, in particular, miss the substantive contribution of the shelf seafloor in regulating nutrients and sequestering carbon. Here, we summarise the biogeochemical functioning of the Arctic shelf seafloor before considering how climate change and regional adjustments to human activities may alter its biogeochemical and ecological dynamics, including ecosystem function, carbon burial, or nutrient recycling. We highlight the importance of the Arctic benthic system in mitigating climatic and anthropogenic change and, with a focus on the Barents Sea, offer some observations and our perspectives on future management and policy.
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Ecossistema , Sedimentos Geológicos , Regiões Árticas , Mudança Climática , Camada de GeloRESUMO
Despite being the first homolog of the bacterial RecQ helicase to be identified in humans, the function of RECQL1 remains poorly characterized. Furthermore, unlike other members of the human RECQ family of helicases, mutations in RECQL1 have not been associated with a genetic disease. Here, we identify 2 families with a genome instability disorder that we have named RECON (RECql ONe) syndrome, caused by biallelic mutations in the RECQL gene. The affected individuals had short stature, progeroid facial features, a hypoplastic nose, xeroderma, and skin photosensitivity and were homozygous for the same missense mutation in RECQL1 (p.Ala459Ser), located within its zinc binding domain. Biochemical analysis of the mutant RECQL1 protein revealed that the p.A459S missense mutation compromised its ATPase, helicase, and fork restoration activity, while its capacity to promote single-strand DNA annealing was largely unaffected. At the cellular level, this mutation in RECQL1 gave rise to a defect in the ability to repair DNA damage induced by exposure to topoisomerase poisons and a failure of DNA replication to progress efficiently in the presence of abortive topoisomerase lesions. Taken together, RECQL1 is the fourth member of the RecQ family of helicases to be associated with a human genome instability disorder.
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Neoplasias da Mama , Replicação do DNA , Feminino , Predisposição Genética para Doença , Instabilidade Genômica , Humanos , Mutação , RecQ Helicases/genética , RecQ Helicases/metabolismoRESUMO
Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway, SLF2 and SMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability.
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Proteínas de Ciclo Celular , Microcefalia , Humanos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Microcefalia/genética , Reparo do DNA/genética , Cromossomos/metabolismo , Instabilidade Genômica , Proteínas de Ligação a DNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Cromossômicas não Histona/metabolismoRESUMO
Climate-induced changes in the ocean and sea ice environment of the Arctic are beginning to generate major and rapid changes in Arctic ecosystems, but the effects of directional forcing on the persistence and distribution of species remain poorly understood. Here, we examine the reproductive traits and population dynamics of the bivalve Astarte crenata and sea star Ctenodiscus crispatus across a north-south transect that intersects the polar front in the Barents Sea. Both species present large oocytes indicative of short pelagic or direct development that do not differ in size-frequency between 74.5 and 81.3º latitude. However, despite gametogenic maturity, we found low frequencies of certain size classes within populations that may indicate periodic recruitment failure. We suggest that recruitment of A. crenata could occur periodically when conditions are favorable, while populations of C. crispatus are characterized by episodic recruitment failures. Pyloric caeca indices in C. crispatus show that food uptake is greatest at, and north of, the polar front, providing credence to the view that interannual variations in the quantity and quality of primary production and its flux to the seafloor, linked to the variable extent and thickness of sea ice, are likely to be strong determinants of physiological fitness. Our findings provide evidence that the distribution and long-term survival of species is not only a simple function of adaptive capacity to specific environmental changes, but will also be contingent on the frequency and occurrence of years where environmental conditions support reproduction and settlement.
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Ecosystems and their biota operate on cyclic rhythms, often entrained by predictable, small-scale changes in their natural environment. Recording and understanding these rhythms can detangle the effect of human induced shifts in the climate state from natural fluctuations. In this study, we assess long-term patterns of reproductive investment in the Antarctic sea urchin, Sterechinus neumayeri, in relation to changes in the environment to identify drivers of reproductive processes. Polar marine biota are sensitive to small changes in their environment and so serve as a barometer whose responses likely mirror effects that will be seen on a wider global scale in future climate change scenarios. Our results indicate that seasonal reproductive periodicity in the urchin is underpinned by a multiyear trend in reproductive investment beyond and in addition to, the previously reported 18-24 month gametogenic cycle. Our model provides evidence that annual reproductive investment could be regulated by an endogenous rhythm since environmental factors only accounted for a small proportion of the residual variation in gonad index. This research highlights a need for multiyear datasets and the combination of biological time series data with large-scale climate metrics that encapsulate multi-factorial climate state shifts, rather than using single explanatory variables to inform changes in biological processes.
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Reprodução , Ouriços-do-Mar/fisiologia , Animais , Regiões Antárticas , Mudança Climática , Ecossistema , Feminino , Gametogênese/fisiologia , Masculino , Estações do AnoRESUMO
The adenovirus 12 early region 1B55K (Ad12E1B55K) protein has long been known to cause non-random damage to chromosomes 1 and 17 in human cells. These sites, referred to as Ad12 modification sites, have marked similarities to classic fragile sites. In the present report we have investigated the effects of Ad12E1B55K on the cellular DNA damage response and on DNA replication, considering our increased understanding of the pathways involved. We have compared human skin fibroblasts expressing Ad12E1B55K (55K+HSF), but no other viral proteins, with the parental cells. Appreciable chromosomal damage was observed in 55K+HSFs compared to parental cells. Similarly, an increased number of micronuclei was observed in 55K+HSFs, both in cycling cells and after DNA damage. We compared DNA replication in the two cell populations; 55K+HSFs showed increased fork stalling and a decrease in fork speed. When replication stress was introduced with hydroxyurea the percentage of stalled forks and replication speeds were broadly similar, but efficiency of fork restart was significantly reduced in 55K+HSFs. After DNA damage, appreciably more foci were formed in 55K+HSFs up to 48 h post treatment. In addition, phosphorylation of ATM substrates was greater in Ad12E1B55K-expressing cells following DNA damage. Following DNA damage, 55K+HSFs showed an inability to arrest in cell cycle, probably due to the association of Ad12E1B55K with p53. To confirm that Ad12E1B55K was targeting components of the double-strand break repair pathways, co-immunoprecipitation experiments were performed which showed an association of the viral protein with ATM, MRE11, NBS1, DNA-PK, BLM, TOPBP1 and p53, as well as with components of the replisome, MCM3, MCM7, ORC1, DNA polymerase δ, TICRR and cdc45, which may account for some of the observed effects on DNA replication. We conclude that Ad12E1B55K impacts the cellular DNA damage response pathways and the replisome at multiple points through protein-protein interactions, causing genomic instability.
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Proteínas E1B de Adenovirus/metabolismo , Adenovírus Humanos/metabolismo , Dano ao DNA , Instabilidade Genômica , Células Cultivadas , DNA/química , Reparo do DNA , Replicação do DNA , Fibroblastos , Humanos , Conformação de Ácido NucleicoRESUMO
The SRC Kinase Adaptor Phosphoprotein 2 (SKAP2) is a broadly expressed adaptor associated with the control of actin-polymerization, cell migration, and oncogenesis. After activation of different receptors at the cell surface, this dimeric protein serves as a platform for assembling other adaptors such as FYB and some SRC family kinase members, although these mechanisms are still poorly understood. The goal of this study is to map the SKAP2 interactome and characterize which domains or binding motifs are involved in these interactions. This is a prerequisite to finely analyze how these pathways are integrated in the cell machinery and to study their role in cancer and other human diseases when this network of interactions is perturbed. In this work, the domain and the binding motif of fourteen proteins interacting with SKAP2 were precisely defined and a new interactor, FAM102A was discovered. Herein, a fine-tuning between the binding of SRC kinases and their activation was identified. This last process, which depends on SKAP2 dimerization, indirectly affects the binding of FYB protein. Analysis of conformational changes associated with activation/inhibition of SRC family members, presently limited to their effect on kinase activity, is extended to their interactive network, which paves the way for therapeutic development.
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Medusae can be conspicuous and abundant members of seafloor communities in deep-sea benthic boundary layers. The epibenthic trachymedusa, Ptychogastria polaris Allman, 1878 (Hydrozoa: Trachylina: Ptychogastriidae) occurs in the cold, high latitude systems of both the northern and southern hemispheres, with a circumpolar distribution in Arctic and sub-Arctic areas, and disjunct reports of a few individuals from Antarctica. In January-February 2010, during benthic megafaunal photosurveys in three subpolar fjords along the West Antarctic Peninsula (Andvord, Flandres and Barilari Bays), P. polaris was recorded in Antarctic Peninsula waters. The trachymedusa, identified from megacore-collected specimens, was a common component of the epifauna in the sediment floored basins at 436-725 m depths in Andvord and Flandres Bays, reaching densities up to 13 m-2, with mean densities in individual basins ranging from 0.06 to 4.19 m-2. These densities are 2 to 400-fold higher than previously reported for P. polaris in either the Arctic or Antarctic. This trachymedusa had an aggregated distribution, occurring frequently in Andvord Bay, but was often solitary in Flandres Bay, with a distribution not significantly different from random. Epibenthic individuals were similar in size, typically measuring 15-25 mm in bell diameter. A morphologically similar trachymedusa, presumably the same species, was also observed in the water column near the bottom in all three fjords. This benthopelagic form attained abundances of up to 7 m-2 of seafloor; however, most P. polaris (~ 80%), were observed on soft sediments. Our findings indicate that fjords provide a prime habitat for the development of dense populations of P. polaris, potentially resulting from high and varied food inputs to the fjord floors. Because P. polaris resides in the water column and at the seafloor, large P. polaris populations may contribute significantly to pelagic-benthic coupling in the WAP fjord ecosystems.
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Ecossistema , Estuários , Hidrozoários/fisiologia , Animais , Regiões Antárticas , Teorema de Bayes , Baías , Tamanho Corporal , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Geografia , Hidrozoários/anatomia & histologia , Hidrozoários/classificação , Processamento de Imagem Assistida por Computador , Mitocôndrias/enzimologia , Oceanos e Mares , FilogeniaRESUMO
Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined gametocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication.
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Estágios do Ciclo de Vida , Malária Falciparum/parasitologia , Plasmodium falciparum/crescimento & desenvolvimento , Adolescente , Criança , Pré-Escolar , Análise por Conglomerados , Humanos , Estudos Longitudinais , Malária Falciparum/epidemiologia , Malária Falciparum/transmissão , Análise Multivariada , Prevalência , Fatores de Risco , Senegal/epidemiologiaRESUMO
Dengue is a major international public health concern, and the number of outbreaks has escalated greatly. Human migration and international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naïve populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake, and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but "inapparent" was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy and uptake.
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Glacio-marine fjords occur widely at high latitudes and have been extensively studied in the Arctic, where heavy meltwater inputs and sedimentation yield low benthic faunal abundance and biodiversity in inner-middle fjords. Fjord benthic ecosystems remain poorly studied in the subpolar Antarctic, including those in extensive fjords along the West Antarctic Peninsula (WAP). Here we test ecosystem predictions from Arctic fjords on three subpolar, glacio-marine fjords along the WAP. With seafloor photographic surveys we evaluate benthic megafaunal abundance, community structure, and species diversity, as well as the abundance of demersal nekton and macroalgal detritus, in soft-sediment basins of Andvord, Flandres and Barilari Bays at depths of 436-725 m. We then contrast these fjord sites with three open shelf stations of similar depths. Contrary to Arctic predictions, WAP fjord basins exhibited 3 to 38-fold greater benthic megafaunal abundance than the open shelf, and local species diversity and trophic complexity remained high from outer to inner fjord basins. Furthermore, WAP fjords contained distinct species composition, substantially contributing to beta and gamma diversity at 400-700 m depths along the WAP. The abundance of demersal nekton and macroalgal detritus was also substantially higher in WAP fjords compared to the open shelf. We conclude that WAP fjords are important hotspots of benthic abundance and biodiversity as a consequence of weak meltwater influences, low sedimentation disturbance, and high, varied food inputs. We postulate that WAP fjords differ markedly from their Arctic counterparts because they are in earlier stages of climate warming, and that rapid warming along the WAP will increase meltwater and sediment inputs, deleteriously impacting these biodiversity hotspots. Because WAP fjords also provide important habitat and foraging areas for Antarctic krill and baleen whales, there is an urgent need to develop better understanding of the structure, dynamics and climate-sensitivity of WAP subpolar fjord ecosystems.