176 research outputs found

    Seasonal dynamics of endosymbiotic ciliates and nematodes in Dreissena polymorpha

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    Abstract We report the results of a two-year study in the Svisloch River (Minsk, Belarus) on the dynamics of infection in Dreissena polymorpha by nematodes and three ciliate species Conchophthirus acuminatus, Ophryoglena sp., and Ancistrumina limnica. Although these endosymbionts were present in most of the samples, their prevalence and infection intensity differed significantly. C. acuminatus and A. limnica infection intensities in both years of the study had a maximum in summer and were positively correlated with water temperature. In contrast, Ophryoglena sp. and nematode infection intensities were considerably lower in summer versus winter and were negatively correlated with temperature. In the first long-term study to monitor the size and reproductive rate of C. acuminatus, we found that mean length was negatively correlated with temperature and that temperature was positively correlated with asexual reproduction, with a peak of cell division in April as water temperatures increased

    \u3ci\u3eAquastella gen. nov.\u3c/i\u3e: A new genus of saprolegniaceous oomycete rotifer parasites related to \u3ci\u3eAphanomyces\u3c/i\u3e, with unique sporangial outgrowths

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    The oomycete genus Aquastella is described to accommodate two new species of parasites of rotifers observed in Brooktrout Lake, New York State, USA. Three rotifer species – Keratella taurocephala,Polyarthra vulgaris, and Ploesoma truncatum – were infected, and this is the first report of oomycete infection in these species. Aquastella attenuata was specific to K. taurocephala and Aquastella aciculariswas specific to P. vulgaris and P. truncatum. The occurrence of infections correlated with peak host population densities and rotifers were infected in the upper layers of the water column. Sequencing of 18S rRNA and phylogenetic analysis of both species placed them within the order Saprolegniales, in a clade closely related to Aphanomyces. The Aquastella species were morphologically distinct from other rotifer parasites as the developing sporangia penetrated out through the host body following its death to produce unique tapered outgrowths. Aquastella attenuata produced long, narrow, tapering, finger-like outgrowths, whilst A. acicularis produced shorter, spike-like outgrowths. We hypothesize that the outgrowths serve to deter predation and slow descent in the water column. Spore cleavage was intrasporangial with spore release through exit tubes. Aquastella attenuata produced primary zoospores, whereas A. acicularisreleased spherical primary aplanospores, more typical of other genera in the Aphanomyces clade

    ELF5 modulates the estrogen receptor cistrome in breast cancer.

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    Acquired resistance to endocrine therapy is responsible for half of the therapeutic failures in the treatment of breast cancer. Recent findings have implicated increased expression of the ETS transcription factor ELF5 as a potential modulator of estrogen action and driver of endocrine resistance, and here we provide the first insight into the mechanisms by which ELF5 modulates estrogen sensitivity. Using chromatin immunoprecipitation sequencing we found that ELF5 binding overlapped with FOXA1 and ER at super enhancers, enhancers and promoters, and when elevated, caused FOXA1 and ER to bind to new regions of the genome, in a pattern that replicated the alterations to the ER/FOXA1 cistrome caused by the acquisition of resistance to endocrine therapy. RNA sequencing demonstrated that these changes altered estrogen-driven patterns of gene expression, the expression of ER transcription-complex members, and 6 genes known to be involved in driving the acquisition of endocrine resistance. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, and proximity ligation assays, we found that ELF5 interacted physically with members of the ER transcription complex, such as DNA-PKcs. We found 2 cases of endocrine-resistant brain metastases where ELF5 levels were greatly increased and ELF5 patterns of gene expression were enriched, compared to the matched primary tumour. Thus ELF5 alters ER-driven gene expression by modulating the ER/FOXA1 cistrome, by interacting with it, and by modulating the expression of members of the ER transcriptional complex, providing multiple mechanisms by which ELF5 can drive endocrine resistance

    Fiber Supplements Derived From Sugarcane Stem, Wheat Dextrin and Psyllium Husk Have Different In Vitro Effects on the Human Gut Microbiota

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    There is growing public interest in the use of fiber supplements as a way of increasing dietary fiber intake and potentially improving the gut microbiota composition and digestive health. However, currently there is limited research into the effects of commercially available fiber supplements on the gut microbiota. Here we used an in vitro human digestive and gut microbiota model system to investigate the effect of three commercial fiber products; NutriKane™, Benefiber® and Psyllium husk (Macro) on the adult gut microbiota. The 16S rRNA gene amplicon sequencing results showed dramatic fiber-dependent changes in the gut microbiota structure and composition. Specific bacterial OTUs within the families Bacteroidaceae, Porphyromonadaceae, Ruminococcaceae, Lachnospiraceae, and Bifidobacteriaceae showed an increase in the relative abundances in the presence of one or more fiber product(s), while Enterobacteriaceae and Pseudomonadaceae showed a reduction in the relative abundances upon addition of all fiber treatments compared to the no added fiber control. Fiber-specific increases in SCFA concentrations showed correlation with the relative abundance of potential SCFA-producing gut bacteria. The chemical composition, antioxidant potential and polyphenolic content profiles of each fiber product were determined and found to be highly variable. Observed product-specific variations could be linked to differences in the chemical composition of the fiber products. The general nature of the fiber-dependent impact was relatively consistent across the individuals, which may demonstrate the potential of the products to alter the gut microbiota in a similar, and predictable direction, despite variability in the starting composition of the individual gut microbiota

    LINE-1 ORF2p expression is nearly imperceptible in human cancers

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    Background Long interspersed element-1 (LINE-1, L1) is the major driver of mobile DNA activity in modern humans. When expressed, LINE-1 loci produce bicistronic transcripts encoding two proteins essential for retrotransposition, ORF1p and ORF2p. Many types of human cancers are characterized by L1 promoter hypomethylation, L1 transcription, L1 ORF1p protein expression, and somatic L1 retrotransposition. ORF2p encodes the endonuclease and reverse transcriptase activities required for L1 retrotransposition. Its expression is poorly characterized in human tissues and cell lines. Results We report mass spectrometry-based tumor proteome profiling studies wherein ORF2p eludes detection. To test whether ORF2p could be detected with specific reagents, we developed and validated five rabbit monoclonal antibodies with immunoreactivity for specific epitopes on the protein. These reagents readily detect ectopic ORF2p expressed from bicistronic L1 constructs. However, endogenous ORF2p is not detected in human tumor samples or cell lines by western blot, immunoprecipitation, or immunohistochemistry despite high levels of ORF1p expression. Moreover, we report endogenous ORF1p-associated interactomes, affinity isolated from colorectal cancers, wherein we similarly fail to detect ORF2p. These samples include primary tumors harboring hundreds of somatically acquired L1 insertions. The new data are available via ProteomeXchange with identifier PXD013743. Conclusions Although somatic retrotransposition provides unequivocal genetic evidence for the expression of ORF2p in human cancers, we are unable to directly measure its presence using several standard methods. Experimental systems have previously indicated an unequal stoichiometry between ORF1p and ORF2p, but in vivo, the expression of these two proteins may be more strikingly uncoupled. These findings are consistent with observations that ORF2p is not tolerable for cell growth

    Validity of Type D personality in Iceland: association with disease severity and risk markers in cardiac patients

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    Type D personality has been associated with poor prognosis in cardiac patients. This study investigated the validity of the Type D construct in Iceland and its association with disease severity and health-related risk markers in cardiac patients. A sample of 1,452 cardiac patients completed the Type D scale (DS14), and a subgroup of 161 patients completed measurements for the five-factor model of personality, emotional control, anxiety, depression, stress and lifestyle factors. The Icelandic DS14 had good psychometric properties and its construct validity was confirmed. Prevalence of Type D was 26–29%, and assessment of Type D personality was not confounded by severity of underlying coronary artery disease. Regarding risk markers, Type D patients reported more psychopharmacological medication use and smoking, but frequency of previous mental problems was similar across groups. Type D is a valid personality construct in Iceland, and is associated with health-related risk markers, but not cardiac disease severity

    Human Macrophages Infected with a High Burden of ESAT-6-Expressing M. tuberculosis Undergo Caspase-1- and Cathepsin B-Independent Necrosis

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    Mycobacterium tuberculosis (Mtb) infects lung macrophages, which instead of killing the pathogen can be manipulated by the bacilli, creating an environment suitable for intracellular replication and spread to adjacent cells. The role of host cell death during Mtb infection is debated because the bacilli have been shown to be both anti-apoptotic, keeping the host cell alive to avoid the antimicrobial effects of apoptosis, and pro-necrotic, killing the host macrophage to allow infection of neighboring cells. Since mycobacteria activate the NLRP3 inflammasome in macrophages, we investigated whether Mtb could induce one of the recently described inflammasome-linked cell death modes pyroptosis and pyronecrosis. These are mediated through caspase-1 and cathepsin-B, respectively. Human monocyte-derived macrophages were infected with virulent (H37Rv) Mtb at a multiplicity of infection (MOI) of 1 or 10. The higher MOI resulted in strongly enhanced release of IL-1β, while a low MOI gave no IL-1β response. The infected macrophages were collected and cell viability in terms of the integrity of DNA, mitochondria and the plasma membrane was determined. We found that infection with H37Rv at MOI 10, but not MOI 1, over two days led to extensive DNA fragmentation, loss of mitochondrial membrane potential, loss of plasma membrane integrity, and HMGB1 release. Although we observed plasma membrane permeabilization and IL-1β release from infected cells, the cell death induced by Mtb was not dependent on caspase-1 or cathepsin B. It was, however, dependent on mycobacterial expression of ESAT-6. We conclude that as virulent Mtb reaches a threshold number of bacilli inside the human macrophage, ESAT-6-dependent necrosis occurs, activating caspase-1 in the process
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