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Tropical river deltas, and the social-ecological systems they sustain, are changing rapidly due to anthropogenic activity and climatic change. Baseline data to inform sustainable management options for resilient deltas is urgently needed and palaeolimnology (reconstructing past conditions from lake or wetland deposits) can provide crucial long-term perspectives needed to identify drivers and rates of change. We review how palaeolimnology can be a valuable tool for resource managers using three current issues facing tropical delta regions: hydrology and sediment supply, salinisation and nutrient pollution. The unique ability of palaeolimnological methods to untangle multiple stressors is also discussed. We demonstrate how palaeolimnology has been used to understand each of these issues, in other aquatic environments, to be incorporated into policy. Palaeolimnology is a key tool to understanding how anthropogenic influences interact with other environmental stressors, providing policymakers and resource managers with a 'big picture' view and possible holistic solutions that can be implemented.
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Recent investigation of a constitutively active ADAMTS13 variant (caADAMTS13) in murine models of acute ischaemic stroke (AIS) have revealed a potential anti-inflammatory mechanism of action contributing to its protective effect. However, it remains unclear whether these observations are a direct result of VWF proteolysis by caADAMTS13. We have implemented state of the art in vitro assays of neutrophil rolling and transmigration to quantify the impact of caADAMTS13 on these processes. Moreover, we have tested caADAMTS13 in two in vivo assays of neutrophil migration to confirm the impact of the treatment on the neutrophil response to sterile inflammation. Neutrophil rolling, over an interleukin-1ß stimulated hCMEC/D3 monolayer, is directly inhibited by caADAMTS13, reducing the proportion of neutrophils rolling to 9.5 ± 3.8â¯% compared to 18.0 ± 4.5â¯% in untreated controls. Similarly, neutrophil transmigration recorded in real-time, was significantly suppressed in the presence of caADAMTS13 which reduced the number of migration events to a level like that in unstimulated controls (18.0 ± 4.5 and 15.8 ± 7.5 cells/mm2/h, respectively). Brain tissue from mice undergoing experimental focal cerebral ischaemia has indicated the inhibition of this process by caADAMTS13. This is supported by caADAMTS13's ability to reduce neutrophil migration into the peritoneal cavity in an ischaemia-independent model of sterile inflammation, with the VWF-dependent mechanism by which this occurs being confirmed using a second experimental stroke model. These findings will be an important consideration in the further development of caADAMTS13 as a potential therapy for AIS and other thromboinflammatory pathologies, including cardiovascular disease.
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Due to the depositional environment, river deltas are said to act as filters and sinks for pollutants. However, many deltas are also densely populated and rapidly urbanizing, creating new and increased sources of pollutants. These sources pose the risk of tipping these environments from pollution sinks to sources, to the world's oceans. We provide detailed seasonal and annual assessments of metal contaminants in riverine suspended particulate matter (SPM) across the densely populated Red River Delta (RRD), Vietnam. The global contributions of elements from the RRD are all <0.2% with many elemental fluxes <0.01%, suggesting the RRD is not a major source of elemental pollution to the ocean. However, 'hotspots' of metal pollution due to human activity and the impacts of tropical storm Son Tinh (July 2018) exceed both national level regulations and international measures of toxicity (e.g. enrichment factors). There is widespread 'extreme pollution' of Cd (enrichment factor >40) and concentrations of As higher than national regulation limits (>17 mg/Kg) at all sites other than one upstream, agricultural-dominated tributary in the dry season. These 'hotspots' are characterised by high inputs of organic matter (e.g. manure fertiliser and urban wastewater), which influences elemental mobility in the particulate and dissolved phases, and are potentially significant sources of pollution downstream. In addition, in the marine and fresh water mixing zone, salinity effects metal complexation with organic matter increasing metals in the particulate phase. Our calculations indicate that the delta is currently acting as a pollutant sink (as determined by high levels of pollutant deposition â¼50%). However, increased in-washing of pollutants and future projected increases in monsoon intensity, saline intrusion, and human activity could shift the delta to become a source of toxic metals. We show the importance of monitoring environmental parameters (primarily dissolved organic matter and salinity) in the RRD to assess the risk of transport and accumulation of toxic metals in the delta sediments, which can lead to net-increases in anthropogenic pollution in the coastal zone and the incorporation of toxic elements in the food chain.
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Metais Pesados , Oligoelementos , Poluentes Químicos da Água , Cádmio , Monitoramento Ambiental , Fertilizantes , Sedimentos Geológicos , Humanos , Esterco , Metais Pesados/análise , Material Particulado , Oligoelementos/análise , Vietnã , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
INTRODUCTION: Stroke is characterized by deleterious oxidative stress. Selenoprotein enzymes are essential endogenous antioxidants, and detailed insight into their role after stroke could define new therapeutic treatments. This systematic review aimed to elucidate how blood selenoprotein concentration and activity change in the acute phase of stroke. METHODS: We searched PubMed, EMBASE, and Medline databases for studies measuring serial blood selenoprotein concentration or activity in acute stroke patients or in stroke patients compared to non-stroke controls. Meta-analyses of studies stratified by the type of stroke, blood compartment, and type of selenoprotein measurement were conducted. RESULTS: Eighteen studies and data from 941 stroke patients and 708 non-stroke controls were included in this review. Glutathione peroxidase (GPx) was the only identified selenoprotein, and its activity was most frequently measured. Results from 12 studies and 693 patients showed that compared to non-stroke controls in acute ischaemic stroke patients, the GPx activity increased in haemolysate (standardized mean difference [SMD]: 0.27, 95% CI: 0.07-0.47) but decreased in plasma (mean difference [MD]: -1.08 U/L, 95% CI: -1.94 to -0.22) and serum (SMD: -0.54, 95% CI: -0.91 to -0.17). From 4 identified studies in 106 acute haemorrhagic stroke patients, the GPx activity decreased in haemolysate (SMD: -0.40, 95% CI: -0.68 to -0.13) and remained unchanged in plasma (MD: -0.10 U/L, 95% CI: -0.81 to 0.61) and serum (MD: -5.00 U/mL, 95% CI: -36.17 to 26.17) compared to non-stroke controls. Results from studies assessing the GPx activity in the haemolysate compartment were inconsistent and characterized by high heterogeneity. CONCLUSIONS: Our results suggest a reduction of the blood GPx activity in acute ischaemic stroke patients, a lack of evidence regarding a role for GPx in haemorrhagic stroke patients, and insufficient evidence for other selenoproteins.
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Isquemia Encefálica , Acidente Vascular Cerebral Hemorrágico , AVC Isquêmico , Selenoproteínas , Antioxidantes , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Glutationa Peroxidase , Acidente Vascular Cerebral Hemorrágico/diagnóstico , Acidente Vascular Cerebral Hemorrágico/patologia , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/patologia , Selênio , Selenoproteínas/metabolismoRESUMO
The axial skeleton of tetrapods is organized into distinct anteroposterior regions of the vertebral column (cervical, trunk, sacral, and caudal), and transitions between these regions are determined by colinear anterior expression boundaries of Hox5/6, -9, -10, and -11 paralogy group genes within embryonic paraxial mesoderm. Fishes, conversely, exhibit little in the way of discrete axial regionalization, and this has led to scenarios of an origin of Hox-mediated axial skeletal complexity with the evolutionary transition to land in tetrapods. Here, combining geometric morphometric analysis of vertebral column morphology with cell lineage tracing of hox gene expression boundaries in developing embryos, we recover evidence of at least five distinct regions in the vertebral skeleton of a cartilaginous fish, the little skate (Leucoraja erinacea). We find that skate embryos exhibit tetrapod-like anteroposterior nesting of hox gene expression in their paraxial mesoderm, and we show that anterior expression boundaries of hox5/6, hox9, hox10, and hox11 paralogy group genes predict regional transitions in the differentiated skate axial skeleton. Our findings suggest that hox-based axial skeletal regionalization did not originate with tetrapods but rather has a much deeper evolutionary history than was previously appreciated.
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Padronização Corporal/fisiologia , Genes Homeobox/genética , Genes Homeobox/fisiologia , Proteínas de Homeodomínio/metabolismo , Rajidae/embriologia , Rajidae/genética , Animais , Evolução Biológica , Padronização Corporal/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Rajidae/fisiologia , Coluna Vertebral/crescimento & desenvolvimento , Coluna Vertebral/metabolismoRESUMO
Apicomplexan infections cause substantial morbidity and mortality, worldwide. New, improved therapies are needed. Herein, we create a next generation anti-apicomplexan lead compound, JAG21, a tetrahydroquinolone, with increased sp3-character to improve parasite selectivity. Relative to other cytochrome b inhibitors, JAG21 has improved solubility and ADMET properties, without need for pro-drug. JAG21 significantly reduces Toxoplasma gondii tachyzoites and encysted bradyzoites in vitro, and in primary and established chronic murine infections. Moreover, JAG21 treatment leads to 100% survival. Further, JAG21 is efficacious against drug-resistant Plasmodium falciparum in vitro. Causal prophylaxis and radical cure are achieved after P. berghei sporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria.
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Parasitos , Toxoplasma , Toxoplasmose , Animais , Camundongos , Plasmodium falciparumRESUMO
Seed size shapes plant evolution and ecosystems, and may be driven by plant size and architecture, dispersers, habitat and insularity. How these factors influence the evolution of giant seeds is unclear, as are the rate of evolution and the biogeographical consequences of giant seeds. We generated DNA and seed size data for the palm tribe Borasseae (Arecaceae) and its relatives, which show a wide diversity in seed size and include the double coconut (Lodoicea maldivica), the largest seed in the world. We inferred their phylogeny, dispersal history and rates of change in seed size, and evaluated the possible influence of plant size, inflorescence branching, habitat and insularity on these changes. Large seeds were involved in 10 oceanic dispersals. Following theoretical predictions, we found that: taller plants with fewer-branched inflorescences produced larger seeds; seed size tended to evolve faster on islands (except Madagascar); and seeds of shade-loving Borasseae tended to be larger. Plant size and inflorescence branching may constrain seed size in Borasseae and their relatives. The possible roles of insularity, habitat and dispersers are difficult to disentangle. Evolutionary contingencies better explain the gigantism of the double coconut than unusually high rates of seed size increase.
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Arecaceae , Dispersão de Sementes , Cocos , Ecossistema , Madagáscar , Sementes/genéticaRESUMO
Low frequency components (i.e. a low pitch (F0) and low formant spacing (ΔF)) signal high salivary testosterone and height in adult male voices and are associated with high masculinity attributions by unfamiliar listeners (in both men and women). However, the relation between the physiological, acoustic and perceptual dimensions of speakers' masculinity prior to puberty remains unknown. In this study, 110 pre-pubertal children (58 girls), aged 3 to 10, were recorded as they described a cartoon picture. 315 adults (182 women) rated children's perceived masculinity from the voice only after listening to the speakers' audio recordings. On the basis of their voices alone, boys who had higher salivary testosterone levels were rated as more masculine and the relation between testosterone and perceived masculinity was partially mediated by F0. The voices of taller boys were also rated as more masculine, but the relation between height and perceived masculinity was not mediated by the considered acoustic parameters, indicating that acoustic cues other than F0 and ΔF may signal stature. Both boys and girls who had lower F0, were also rated as more masculine, while ΔF did not affect ratings. These findings highlight the interdependence of physiological, acoustic and perceptual dimensions, and suggest that inter-individual variation in male voices, particularly F0, may advertise hormonal masculinity from a very early age.
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Desenvolvimento Infantil/fisiologia , Masculinidade , Percepção Social , Acústica da Fala , Voz/fisiologia , Adolescente , Adulto , Fatores Etários , Percepção Auditiva/fisiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fatores Sexuais , Maturidade Sexual/fisiologia , Testosterona/sangue , Adulto JovemRESUMO
The relative influence of niche vs. neutral processes in ecosystem dynamics is an on-going debate, but the extent to which they structured the earliest animal communities is unknown. Some of the oldest known metazoan-dominated paleocommunities occur in Ediacaran age (~ 565 million years old) strata in Newfoundland, Canada and Charnwood Forest, UK. These comprise large and diverse populations of sessile organisms that are amenable to spatial point process analyses, enabling inference of the most likely underlying niche or neutral processes governing community structure. We mapped seven Ediacaran paleocommunities using LiDAR, photogrammetry and a laser line probe. We found that neutral processes dominate these paleocommunities, with niche processes exerting limited influence, in contrast with the niche-dominated dynamics of modern marine ecosystems. The dominance of neutral processes suggests that early metazoan diversification may not have been driven by systematic adaptations to the local environment, but instead may have resulted from stochastic demographic differences.
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Ecossistema , Florestas , Animais , CanadáRESUMO
Pre-pubertal boys and girls speak with acoustically different voices despite the absence of a clear anatomical dimorphism in the vocal apparatus, suggesting that a strong component of the expression of gender through the voice is behavioural. Initial evidence for this hypothesis was found in a previous study showing that children can alter their voice to sound like a boy or like a girl. However, whether they can spontaneously modulate these voice components within their own gender in order to vary the expression of their masculinity and femininity remained to be investigated. Here, seventy-two English-speaking children aged 6-10 were asked to give voice to child characters varying in masculine and feminine stereotypicality to investigate whether primary school children spontaneously adjust their sex-related cues in the voice-fundamental frequency (F0) and formant spacing (ΔF)-along gender stereotypical lines. Boys and girls masculinized their voice, by lowering F0 and ΔF, when impersonating stereotypically masculine child characters of the same sex. Girls and older boys also feminized their voice, by raising their F0 and ΔF, when impersonating stereotypically feminine same-sex child characters. These findings reveal that children have some knowledge of the sexually dimorphic acoustic cues underlying the expression of gender, and are capable of controlling them to modulate gender-related attributes, paving the way for the use of the voice as an implicit, objective measure of the development of gender stereotypes and behaviour.