Outbreaks of fatal leukemia-like cancers of marine bivalves throughout the world have led to massive population loss. The cause of the disease is unknown. We recently identified a retrotransposon, ...Steamer, that is highly expressed and amplified to high copy number in neoplastic cells of soft-shell clams (Mya arenaria). Through analysis of Steamer integration sites, mitochondrial DNA single-nucleotide polymorphisms (SNPs), and polymorphic microsatellite alleles, we show that the genotypes of neoplastic cells do not match those of the host animal. Instead, neoplastic cells from dispersed locations in New York, Maine, and Prince Edward Island (PEI), Canada, all have nearly identical genotypes that differ from those of the host. These results indicate that the cancer is spreading between animals in the marine environment as a clonal transmissible cell derived from a single original clam. Our findings suggest that horizontal transmission of cancer cells is more widespread in nature than previously supposed.
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•Clam leukemia genotypes are distinct from their hosts and nearly identical to each other•The transmissible cancer clone likely arose in a single individual•Clam leukemia is transmitted horizontally between animals as contagious cancer cells•Contagious cancer cell transmission may be widespread in the marine environment
A fatal form of cancer is spreading between animals in the marine environment as a clonal horizontally transmissible cell, likely derived from a single original clam.
Summary Background The relation between platelet reactivity and stent thrombosis, major bleeding, and other adverse events after coronary artery implantation of drug-eluting stents has been ...incompletely characterised. We aimed to determine the relation between platelet reactivity during dual therapy with aspirin and clopidogrel and clinical outcomes after successful coronary drug-eluting stent implantation. Methods ADAPT-DES was a prospective, multicentre registry of patients successfully treated with one or more drug-eluting stents and given aspirin and clopidogrel at 10–15 US and European hospitals. We assessed platelet reactivity in those patients after successful percutaneous coronary intervention using VerifyNow point-of-care assays, and assigned different cutoffs to define high platelet reactivity. The primary endpoint was definite or probable stent thrombosis; other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. We did a propensity-adjusted multivariable analysis to determine the relation between platelet reactivity and subsequent adverse events. This study is registered with ClinicalTrials.gov , number NCT00638794. Findings Between Jan 7, 2008, and Sept 16, 2010, 8665 patients were prospectively enrolled at 11 sites, of which 8582 were eligible. At 1-year follow-up, stent thrombosis had occurred in 70 (0·8%) patients, myocardial infarction in 269 (3·1%), clinically relevant bleeding in 531 (6·2%), and death in 161 (1·9%) patients. High platelet reactivity on clopidogrel was strongly related to stent thrombosis (adjusted HR 2·49 95% CI 1·43–4·31, p=0·001) and myocardial infarction (adjusted HR 1·42 1·09–1·86, p=0·01), was inversely related to bleeding (adjusted HR 0·73 0·61–0·89, p=0·002), but was not related to mortality (adjusted HR 1·20 0·85–1·70, p=0·30). High platelet reactivity on aspirin was not significantly associated with stent thrombosis (adjusted HR 1·46 0·58–3·64, p=0·42), myocardial infarction, or death, but was inversely related to bleeding (adjusted HR 0·65 0·43–0·99, p=0·04). Interpretation The findings from this study emphasise the counter-balancing effects of haemorrhagic and ischaemic complications after stent implantation, and suggest that safer drugs or tailored strategies for the use of more potent agents must be developed if the benefits of greater platelet inhibition in patients with cardiovascular disease are to be realised. Funding Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano, and Accumetrics
Most cancers arise from oncogenic changes in the genomes of somatic cells, and while the cells may migrate by metastasis, they remain within that single individual. Natural transmission of cancer ...cells from one individual to another has been observed in two distinct cases in mammals (Tasmanian devils and dogs), but these are generally considered to be rare exceptions in nature. The discovery of transmissible cancer in soft-shell clams (Mya arenaria) suggested that this phenomenon might be more widespread. Here we analyse disseminated neoplasia in mussels (Mytilus trossulus), cockles (Cerastoderma edule), and golden carpet shell clams (Polititapes aureus) and find that neoplasias in all three species are attributable to independent transmissible cancer lineages. In mussels and cockles, the cancer lineages are derived from their respective host species; however, unexpectedly, cancer cells in P. aureus are all derived from Venerupis corrugata, a different species living in the same geographical area. No cases of disseminated neoplasia have thus far been found in V. corrugata from the same region. These findings show that transmission of cancer cells in the marine environment is common in multiple species, that it has originated many times, and that while most transmissible cancers are found spreading within the species of origin, cross-species transmission of cancer cells can occur.
Michael J. Metzger * E-mail: mm4184@columbia.edu Affiliations Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, United States of America, Howard Hughes ...Medical Institute, New York, New York, United States of America Stephen P. Goff Affiliations Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, United States of America, Howard Hughes Medical Institute, New York, New York, United States of America, Department of Microbiology and Immunology, Columbia University, New York, New York, United States of AmericaCitation: Metzger MJ, Goff SP (2016) A Sixth Modality of Infectious Disease: Contagious Cancer from Devils to Clams and Beyond. While experimentally transplanted CTVT usually regresses after a few months, naturally acquired disease does not always regress 2. ...these cells have been evolving and spreading as an asexual parasitic organism that has outlived its original canine host by more than 500 generations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background The incidence, predictors, and prognostic impact of post-discharge bleeding (PDB) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation are ...unclear. Objectives This study sought to characterize the determinants and consequences of PDB after PCI. Methods The prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study was used to determine the incidence and predictors of clinically relevant bleeding events occurring within 2 years after hospital discharge. The effect of PDB on subsequent 2-year all-cause mortality was estimated by time-adjusted Cox proportional hazards regression. Results Among 8,582 “all-comers” who underwent successful PCI with DES in the ADAPT-DES study, PDB occurred in 535 of 8,577 hospital survivors (6.2%) at a median time of 300 days (interquartile range: 130 to 509 days) post-discharge. Gastrointestinal bleeding (61.7%) was the most frequent source of PDB. Predictors of PDB included older age, lower baseline hemoglobin, lower platelet reactivity on clopidogrel, and use of chronic oral anticoagulation therapy. PDB was associated with higher crude rates of all-cause mortality (13.0% vs. 3.2%; p < 0.0001). Following multivariable adjustment, PDB was strongly associated with 2-year mortality (hazard ratio HR: 5.03; p < 0.0001), with an effect size greater than that of post-discharge myocardial infarction (PDMI) (HR: 1.92; p = 0.009). Conclusions After successful PCI with DES in an unrestricted patient population, PDB is not uncommon and has a strong relationship with subsequent all-cause mortality, greater that that associated with PDMI. Efforts to reduce PDB may further improve prognosis after successful DES implantation. (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents ADAPT-DES; NCT00638794 )
Abstract
Financial sector wages have increased extraordinarily over the last decades. We address two potential explanations for this increase: (1) rising demand for talent and (2) firms sharing rents ...with their employees. Matching administrative data of Swedish workers, which include unique measures of individual talent, with financial information on their employers, we find no evidence that talent in finance improved, neither on average nor at the top. The increase in relative finance wages is present across talent and education levels, which together can explain at most 20% of it. In contrast, rising financial sector profits that are shared with employees account for up to half of the relative wage increase. The limited labour supply response may partly be explained by the importance of early-career entry and social connections in finance. Our findings alleviate concerns about “brain drain” into finance but suggest that finance workers have captured rising rents over time.
It has become increasingly clear that retrotransposons (RTEs) are more widely expressed in somatic tissues than previously appreciated. RTE expression has been implicated in a myriad of biological ...processes ranging from normal development and aging, to age related diseases such as cancer and neurodegeneration. Long Terminal Repeat (LTR)-RTEs are evolutionary ancestors to, and share many features with, exogenous retroviruses. In fact, many organisms contain endogenous retroviruses (ERVs) derived from exogenous retroviruses that integrated into the germ line. These ERVs are inherited in Mendelian fashion like RTEs, and some retain the ability to transmit between cells like viruses, while others develop the ability to act as RTEs. The process of evolutionary transition between LTR-RTE and retroviruses is thought to involve multiple steps by which the element loses or gains the ability to transmit copies between cells versus the ability to replicate intracellularly. But, typically, these two modes of transmission are incompatible because they require assembly in different sub-cellular compartments. Like murine IAP/IAP-E elements, the gypsy family of retroelements in arthropods appear to sit along this evolutionary transition. Indeed, there is some evidence that gypsy may exhibit retroviral properties. Given that gypsy elements have been found to actively mobilize in neurons and glial cells during normal aging and in models of neurodegeneration, this raises the question of whether gypsy replication in somatic cells occurs via intracellular retrotransposition, intercellular viral spread, or some combination of the two. These modes of replication in somatic tissues would have quite different biological implications. Here, we demonstrate that Drosophila gypsy is capable of both cell-associated and cell-free viral transmission between cultured S2 cells of somatic origin. Further, we demonstrate that the ability of gypsy to move between cells is dependent upon a functional copy of its viral envelope protein. This argues that the gypsy element has transitioned from an RTE into a functional endogenous retrovirus with the acquisition of its envelope gene. On the other hand, we also find that intracellular retrotransposition of the same genomic copy of gypsy can occur in the absence of the Env protein. Thus, gypsy exhibits both intracellular retrotransposition and intercellular viral transmission as modes of replicating its genome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable ...adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant protein F1-V alone and MPLA-adjuvanted F1-V, the nanoparticle-based vaccination regimen induced an immune response that was characterized by high titer and high avidity IgG1 anti-F1-V antibody that persisted for at least 23 weeks post-vaccination. After challenge, no Y. pestis were recovered from the lungs, livers, or spleens of mice vaccinated with the nanoparticle-based formulation and histopathological appearance of lung, liver, and splenic tissues from these mice post-vaccination was remarkably similar to uninfected control mice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bivalves, from raw oysters to steamed clams, are popular choices among seafood lovers and once limited to the coastal areas. The rapid growth of the aquaculture industry and improvement in the ...preservation and transport of seafood have enabled them to be readily available anywhere in the world. Over the years, oysters, mussels, scallops, and clams have been the focus of research for improving the production, managing resources, and investigating basic biological and ecological questions. During this decade, an impressive amount of information using high-throughput genomic, transcriptomic and proteomic technologies has been produced in various classes of the Mollusca group, and it is anticipated that basic and applied research will significantly benefit from this resource. One aspect that is also taking momentum is the use of bivalves as a model system for human health. In this review, we highlight some of the aspects of the biology of bivalves that have direct implications in human health including the shell formation, stem cells and cell differentiation, the ability to fight opportunistic and specific pathogens in the absence of adaptive immunity, as source of alternative drugs, mucosal immunity and, microbiome turnover, toxicology, and cancer research. There is still a long way to go; however, the next time you order a dozen oysters at your favorite raw bar, think about a tasty model organism that will not only please your palate but also help unlock multiple aspects of molluscan biology and improve human health.
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•Bivalves as a model system for human health.•Mucosal immunity in invertebrates.•HABs and bivalves to learn about elimination of toxins.•Stem cells in invertebrates.•Oncogenic mechanisms and bivalve transmissible neoplasia.
Island Biogeography Reveals the Deep History of SIV Worobey, Michael; Telfer, Paul; Souquière, Sandrine ...
Science (American Association for the Advancement of Science),
09/2010, Letnik:
329, Številka:
5998
Journal Article
Recenzirano
Simian immunodeficiency virus (SIV) lineages have been identified that are endemic to Bioko Island. The time the island formed offers a geological time scale calibration point for dating the most ...recent common ancestor of SIV. The Bioko viruses cover the whole range of SIV genetic diversity, and each Bioko SIV clade is most closely related to viruses circulating in hosts of the same genus on the African mainland rather than to SIVs of other Bioko species. Our phylogeographic approach establishes that SIV is ancient and at least 32,000 years old. Our conservative calibration point and analyses of gene sequence saturation and dating bias suggest it may be much older.
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