Multicellularity is often considered a prerequisite for morphological complexity, as seen in the camera-type eyes found in several groups of animals. A notable exception exists in single-celled ...eukaryotes called dinoflagellates, some of which have an eye-like 'ocelloid' consisting of subcellular analogues to a cornea, lens, iris, and retina. These planktonic cells are uncultivated and rarely encountered in environmental samples, obscuring the function and evolutionary origin of the ocelloid. Here we show, using a combination of electron microscopy, tomography, isolated-organelle genomics, and single-cell genomics, that ocelloids are built from pre-existing organelles, including a cornea-like layer made of mitochondria and a retinal body made of anastomosing plastids. We find that the retinal body forms the central core of a network of peridinin-type plastids, which in dinoflagellates and their relatives originated through an ancient endosymbiosis with a red alga. As such, the ocelloid is a chimaeric structure, incorporating organelles with different endosymbiotic histories. The anatomical complexity of single-celled organisms may be limited by the components available for differentiation, but the ocelloid shows that pre-existing organelles can be assembled into a structure so complex that it was initially mistaken for a multicellular eye. Although mitochondria and plastids are acknowledged chiefly for their metabolic roles, they can also be building blocks for greater structural complexity.
We currently have little idea where Mycobacterium tuberculosis (Mtb) transmission occurs in high incidence settings. Molecular studies suggest that only around 8-19% of transmission to adults occurs ...within-household, or between known social-contacts. This contrasts with findings from social-contact studies, which show that substantial proportions of contact time occur in households, workplaces and schools. A mathematical model of social-contact behaviour and Mtb transmission was developed, incorporating variation in susceptibility and infectiousness. Three types of contact were simulated: household, repeated (individuals outside household contacted repeatedly with daily-monthly frequency) and non-repeated. The model was parameterised using data from Cape Town, South Africa, on mean and variance in contact numbers and contact durations, by contact type, and fitted to an estimate of overdispersion in numbers of secondary cases ('superspreading') in Cape Town. Household, repeated, and non-repeated contacts contributed 36%, 13%, and 51% of contact time, and 13%, 8%, and 79% of disease, respectively. Results suggest contact saturation, exacerbated by long disease durations and superspreading, cause the high proportion of transmission between non-repeated contacts. Household and social-contact tracing is therefore unlikely to reach most tuberculosis cases. A better understanding of transmission locations, and methods to identify superspreaders, are urgently required to improve tuberculosis prevention strategies.
Modern microbial mats are potential analogues of some of Earth's earliest ecosystems. Excellent examples can be found in Shark Bay, Australia, with mats of various morphologies. To further our ...understanding of the functional genetic potential of these complex microbial ecosystems, we conducted for the first time shotgun metagenomic analyses. We assembled metagenomic next-generation sequencing data to classify the taxonomic and metabolic potential across diverse morphologies of marine mats in Shark Bay. The microbial community across taxonomic classifications using protein-coding and small subunit rRNA genes directly extracted from the metagenomes suggests that three phyla Proteobacteria, Cyanobacteria and Bacteriodetes dominate all marine mats. However, the microbial community structure between Shark Bay and Highbourne Cay (Bahamas) marine systems appears to be distinct from each other. The metabolic potential (based on SEED subsystem classifications) of the Shark Bay and Highbourne Cay microbial communities were also distinct. Shark Bay metagenomes have a metabolic pathway profile consisting of both heterotrophic and photosynthetic pathways, whereas Highbourne Cay appears to be dominated almost exclusively by photosynthetic pathways. Alternative non-rubisco-based carbon metabolism including reductive TCA cycle and 3-hydroxypropionate/4-hydroxybutyrate pathways is highly represented in Shark Bay metagenomes while not represented in Highbourne Cay microbial mats or any other mat forming ecosystems investigated to date. Potentially novel aspects of nitrogen cycling were also observed, as well as putative heavy metal cycling (arsenic, mercury, copper and cadmium). Finally, archaea are highly represented in Shark Bay and may have critical roles in overall ecosystem function in these modern microbial mats.
The integrity and composition of the tumour microenvironment (TME) is highly plastic, undergoing constant remodelling in response to instructive signals derived from alterations in the availability ...and nature of systemic host factors. This 'systemic milieu' is directly modulated by host exposure to modifiable lifestyle factors such as exercise. Host exposure to regular exercise markedly reduces the risk of the primary development of several cancers and might improve clinical outcomes following a diagnosis of a primary disease. However, the molecular mechanisms that underpin the apparent antitumour effects of exercise are poorly understood. In this Opinion article, we explore the putative effects of exercise in reprogramming the interaction between the host and the TME. Specifically, we speculate on the possible effects of exercise on reprogramming 'distant' tissue microenvironments (those not directly involved in the exercise response) by analysing how alterations in the systemic milieu might modulate key TME components to influence cancer hallmarks.
A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating ...in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March-April 2020. Excess mortality particularly affected ≥ 65 year olds (91% of all excess deaths), but also 45-64 (8%) and 15-44 year olds (1%). No excess mortality was observed in 0-14 year olds.
Bath (UK) is a designated UNESCO World Heritage site. A National Lottery funded Landscape Partnership, Bathscape, seeks to articulate a vision for the city as a Landscape City. Walking the Names ...(2019-21) was a cycle of slow participatory walks reading the names of those who had died of poverty in the Bath Union Workhouse. The site-specific work took place in the burial ground of the nineteenth-century institution where the dead were buried in unmarked graves. The paper reviews the project in the context of the emergence of uneasy memories and silenced voices in the contested spaces of Bath's memory landscape. A walking arts process is presented as slow activism, offering a participatory, corporeal, sensory engagement with landscape, power and memory. Drawing on the vision of the Landscape City, reflecting on the city as 'wounded', the essay explores a co-creative process of embodied critical re-memorialisation generating contemporary resonances.
Patients with immune thrombocytopenia (ITP) who relapse after an initial trial of corticosteroid treatment present a therapeutic challenge. Current guidelines recommend consideration of splenectomy, ...despite the known risks associated with surgery and the postsplenectomy state. To better define these risks, we identified a cohort of 9976 patients with ITP, 1762 of whom underwent splenectomy. The cumulative incidence of abdominal venous thromboembolism (AbVTE) was 1.6% compared with 1% in patients who did not undergo splenectomy; venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus) after splenectomy was 4.3% compared with 1.7% in patients who did not undergo splenectomy. There was increased risk of AbVTE early (<90 days; hazard ratio HR 5.4 confidence interval (CI), 2.3-12.5), but not late (≥90 days; HR 1.5 CI, 0.9-2.6) after splenectomy. There was increased risk of VTE both early (HR 5.2 CI, 3.2-8.5) and late (HR 2.7 CI, 1.9-3.8) after splenectomy. The cumulative incidence of sepsis was 11.1% among the ITP patients who underwent splenectomy and 10.1% among the patients who did not. Splenectomy was associated with a higher adjusted risk of sepsis, both early (HR 3.3 CI, 2.4-4.6) and late (HR 1.6 or 3.1, depending on comorbidities). We conclude that ITP patients post splenectomy are at increased risk for AbVTE, VTE, and sepsis.
•After splenectomy, patients with ITP have a higher risk of venous thrombosis and sepsis than patients with ITP who do not undergo splenectomy.
Melanoma exhibits numerous transcriptional cell states including neural crest-like cells as well as pigmented melanocytic cells. How these different cell states relate to distinct tumorigenic ...phenotypes remains unclear. Here, we use a zebrafish melanoma model to identify a transcriptional program linking the melanocytic cell state to a dependence on lipid droplets, the specialized organelle responsible for lipid storage. Single-cell RNA-sequencing of these tumors show a concordance between genes regulating pigmentation and those involved in lipid and oxidative metabolism. This state is conserved across human melanoma cell lines and patient tumors. This melanocytic state demonstrates increased fatty acid uptake, an increased number of lipid droplets, and dependence upon fatty acid oxidative metabolism. Genetic and pharmacologic suppression of lipid droplet production is sufficient to disrupt cell cycle progression and slow melanoma growth in vivo. Because the melanocytic cell state is linked to poor outcomes in patients, these data indicate a metabolic vulnerability in melanoma that depends on the lipid droplet organelle.
Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral ...communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host-virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.
Summary Background Data on causes of vision impairment and blindness are important for development of public health policies, but comprehensive analysis of change in prevalence over time is lacking. ...Methods We did a systematic analysis of published and unpublished data on the causes of blindness (visual acuity in the better eye less than 3/60) and moderate and severe vision impairment (MSVI visual acuity in the better eye less than 6/18 but at least 3/60) from 1980 to 2012. We estimated the proportions of overall vision impairment attributable to cataract, glaucoma, macular degeneration, diabetic retinopathy, trachoma, and uncorrected refractive error in 1990–2010 by age, geographical region, and year. Findings In 2010, 65% (95% uncertainty interval UI 61–68) of 32·4 million blind people and 76% (73–79) of 191 million people with MSVI worldwide had a preventable or treatable cause, compared with 68% (95% UI 65–70) of 31·8 million and 80% (78–83) of 172 million in 1990. Leading causes worldwide in 1990 and 2010 for blindness were cataract (39% and 33%, respectively), uncorrected refractive error (20% and 21%), and macular degeneration (5% and 7%), and for MSVI were uncorrected refractive error (51% and 53%), cataract (26% and 18%), and macular degeneration (2% and 3%). Causes of blindness varied substantially by region. Worldwide and in all regions more women than men were blind or had MSVI due to cataract and macular degeneration. Interpretation The differences and temporal changes we found in causes of blindness and MSVI have implications for planning and resource allocation in eye care. Funding Bill & Melinda Gates Foundation, Fight for Sight, Fred Hollows Foundation, and Brien Holden Vision Institute.
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