The microbiome of the cosmopolitan diatom leptocylindrus reveals significant spatial and temporal variability

Copyright © 2018 Ajani, Kahlke, Siboni, Carney, Murray and Seymour. The ecological interactions between phytoplankton and marine bacteria have important implications for the productivity and biogeochemistry of ocean ecosystems. In this study we characterized the microbial assemblages associated with multiple isolates of the ecologically important diatom Leptocylindrus using amplicon sequencing of the 16S rRNA gene, to examine levels of conservation of the microbiome across closely related species or strains. We also assessed if the microbiome structure of a given diatom strain was dependent on the location from which it was isolated and if the microbiome of cultured isolates significantly changed overtime from the seawater in which they were isolated. The bacterial assemblages from 36 strains belonging to three species (Leptocylindrus danicus, Leptocylindrus convexus, and Leptocylindrus aporus) isolated from six locations spanning > 1000 km of south east Australian coastline over 1 year, were dominated by the Rhodobacteraceae (∼60%) and the Flavobacteriaceae (∼10%). Across all strains, only one 'core OTU' (Roseovarius sp.) was identified across all samples. We observed no significant differences in bacterial community composition between diatom species. Significant differences in microbiome structure were, however, observed between diatom strains collected at different sampling times and from differing locations, albeit these two factors were coupled. Moreover, while bacterial communities under domestication varied from the seawater in which they were isolated, they remained specific to the location/month of origin, i.e., different regions and time points harbored distinct bacterial communities. Our study delivers new knowledge in relation to diatom-bacterial associations, revealing that the location/time from which a diatom is isolated plays an important role in shaping its microbiome

Aryl Hydrocarbon Receptor–Independent Toxicity of Weathered Crude Oil during Fish Development

Polycyclic aromatic hydrocarbons (PAHs), derived largely from fossil fuels and their combustion, are pervasive contaminants in rivers, lakes, and nearshore marine habitats. Studies after the Exxon Valdez oil spill demonstrated that fish embryos exposed to low levels of PAHs in weathered crude oil develop a syndrome of edema and craniofacial and body axis defects. Although mechanisms leading to these defects are poorly understood, it is widely held that PAH toxicity is linked to aryl hydrocarbon receptor (AhR) binding and cytochrome P450 1A (CYP1A) induction. Using zebrafish embryos, we show that the weathered crude oil syndrome is distinct from the well-characterized AhR-dependent effects of dioxin toxicity. Blockade of AhR pathway components with antisense morpholino oligonucleotides demonstrated that the key developmental defects induced by weathered crude oil exposure are mediated by low-molecular-weight tricyclic PAHs through AhR-independent disruption of cardiovascular function and morphogenesis. These findings have multiple implications for the assessment of PAH impacts on coastal habitats

Carney-Complex: Multiple resections of recurrent cardiac myxoma

We report a case of a female patient who was operated at the third relapse of an atrial myxoma caused by Carney complex. The difficult operation was performed without any complications despite extensive adhesions caused by the previous operations. The further inpatient course went without complications and the patient was discharged to the consecutive treatment on the 9th postoperative day. The echocardiographic finding postoperative showed no abnormalities

Changes in lower limb rotation after soft tissue surgery in spastic diplegia: 3-dimensional gait analysis in 28 children

Background and purpose Rotational osteotomies are usually necessary to correct pronounced rotational deformities in ambulant children with cerebral palsy. The effects of soft tissue surgery on such deformities are unclear. In this retrospective study, we determined whether multilevel soft tissue surgery, performed to correct deformities in the sagittal plane, would also have an effect on rotational parameters

Catechol-O-Methyltransferase Expression and 2-Methoxyestradiol Affect Microtubule Dynamics and Modify Steroid Receptor Signaling in Leiomyoma Cells

CONTEXT: Development of optimal medicinal treatments of uterine leiomyomas represents a significant challenge. 2-Methoxyestradiol (2ME) is an endogenous estrogen metabolite formed by sequential action of CYP450s and catechol-O-methyltransferase (COMT). Our previous study demonstrated that 2ME is a potent antiproliferative, proapoptotic, antiangiogenic, and collagen synthesis inhibitor in human leiomyomas cells (huLM). OBJECTIVES: Our objectives were to investigate whether COMT expression, by the virtue of 2ME formation, affects the growth of huLM, and to explore the cellular and molecular mechanisms whereby COMT expression or treatment with 2ME affect these cells. RESULTS: Our data demonstrated that E(2)-induced proliferation was less pronounced in cells over-expressing COMT or treated with 2ME (500 nM). This effect on cell proliferation was associated with microtubules stabilization and diminution of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) transcriptional activities, due to shifts in their subcellular localization and sequestration in the cytoplasm. In addition, COMT over expression or treatment with 2ME reduced the expression of hypoxia-inducible factor -1alpha (HIF-1 alpha) and the basal level as well as TNF-alpha-induced aromatase (CYP19) expression. CONCLUSIONS: COMT over expression or treatment with 2ME stabilize microtubules, ameliorates E(2)-induced proliferation, inhibits ERalpha and PR signaling, and reduces HIF-1 alpha and CYP19 expression in human uterine leiomyoma cells. Thus, microtubules are a candidate target for treatment of uterine leiomyomas. In addition, the naturally occurring microtubule-targeting agent 2ME represents a potential new therapeutic for uterine leiomyomas

Parasitoid Increases Survival of Its Pupae by Inducing Hosts to Fight Predators

Many true parasites and parasitoids modify the behaviour of their host, and these changes are thought to be to the benefit of the parasites. However, field tests of this hypothesis are scarce, and it is often unclear whether the host or the parasite profits from the behavioural changes, or even if parasitism is a cause or consequence of the behaviour. We show that braconid parasitoids (Glyptapanteles sp.) induce their caterpillar host (Thyrinteina leucocerae) to behave as a bodyguard of the parasitoid pupae. After parasitoid larvae exit from the host to pupate, the host stops feeding, remains close to the pupae, knocks off predators with violent head-swings, and dies before reaching adulthood. Unparasitized caterpillars do not show these behaviours. In the field, the presence of bodyguard hosts resulted in a two-fold reduction in mortality of parasitoid pupae. Hence, the behaviour appears to be parasitoid-induced and confers benefits exclusively to the parasitoid

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk

OBJECTIVE: To describe the association between postmenopausal estrogen-only therapy use and risk of ovarian carcinoma, specifically with regard to disease histotype and duration and timing of use. METHODS: We conducted a pooled analysis of 906 women with ovarian carcinoma and 1,220 women in a control group; all 2,126 women included reported having had a hysterectomy. Ten population-based case-control studies participating in the Ovarian Cancer Association Consortium, an international consortium whose goal is to combine data from many studies with similar methods so reliable assessments of risk factors can be determined, were included. Self-reported questionnaire data from each study were harmonized and conditional logistic regression was used to examine estrogen-only therapy's histotype-specific and duration and recency of use associations. RESULTS: Forty-three and a half percent of the women in the control group reported previous use of estrogen-only therapy. Compared with them, current or recent estrogen-only therapy use was associated with an increased risk for the serous (51.4%, odds ratio [OR] 1.63, 95% confidence interval [CI] 1.27-2.09) and endometrioid (48.6%, OR 2.00, 95% CI 1.17-3.41) histotypes. In addition, statistically significant trends in risk according to duration of use were seen among current or recent postmenopausal estrogen-only therapy users for both ovarian carcinoma histotypes (Ptrend<.001 for serous and endometrioid). Compared with women in the control group, current or recent users for 10 years or more had increased risks of serous ovarian carcinoma (36.8%, OR 1.73, 95% CI 1.26-2.38) and endometrioid ovarian carcinoma (34.9%, OR 4.03, 95% CI 1.91-8.49). CONCLUSION: We found evidence of an increased risk of serous and endometrioid ovarian carcinoma associated with postmenopausal estrogen-only therapy use, particularly of long duration. These findings emphasize that risk may be associated with extended estrogen-only therapy use

AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish

The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TILLING) and predicted to express a non-functional AHR2 protein. We characterized AHR activity in the mutant line using TCDD and leflunomide as toxicological probes to investigate function, ligand binding and CYP1A induction patterns of paralogues AHR2, AHR1A and AHR1B. By evaluating TCDD-induced developmental toxicity, mRNA expression changes and CYP1A protein in the AHR2 mutant line, we determined that ahr2hu3335 zebrafish are functionally null. In silico modeling predicted differential binding of TCDD and leflunomide to the AHR paralogues. AHR1A is considered a non-functional pseudogene as it does not bind TCCD or mediate in vivo TCDD toxicity. Homology modeling, however, predicted a ligand binding conformation of AHR1A with leflunomide. AHR1A-dependent CYP1A immunohistochemical expression in the liver provided in vivo confirmation of the in silico docking studies. The ahr2hu3335 functional knockout line expands the experimental power of zebrafish to unravel the role of the AHR during development, as well as highlights potential activity of the other AHR paralogues in ligand-specific toxicological responses

Tolerability of breast ductal lavage in women from families at high genetic risk of breast cancer

<p>Abstract</p> <p>Background</p> <p>Ductal lavage (DL) has been proposed as a minimally-invasive, well-tolerated tool for obtaining breast epithelial cells for cytological evaluation of breast cancer risk. We report DL tolerability in <it>BRCA1/2 </it>mutation-positive and -negative women from an IRB-approved research study.</p> <p>Methods</p> <p>165 <it>BRCA1/2 </it>mutation-positive, 26 mutation-negative and 3 mutation unknown women underwent mammography, breast MRI and DL. Psychological well-being and perceptions of pain were obtained before and after DL, and compared with pain experienced during other screening procedures.</p> <p>Results</p> <p>The average <b><it>anticipated </it></b>and <b><it>experienced </it></b>discomfort rating for DL, 47 and 48 (0–100), were significantly higher (<it>p </it>< 0.01) than the <b><it>anticipated </it></b>and <b><it>experienced </it></b>discomfort of mammogram (38 and 34), MRI (36 and 25) or nipple aspiration (42 and 27). Women with greater pre-existing emotional distress experienced more DL-related discomfort than they anticipated. Women reporting DL-related pain as worse than expected were nearly three times more likely to refuse subsequent DL than those reporting it as the same or better than expected. Twenty-five percent of participants refused repeat DL at first annual follow-up.</p> <p>Conclusion</p> <p>DL was anticipated to be and experienced as <b>more </b>uncomfortable than other procedures used in breast cancer screening. Higher underlying psychological distress was associated with decreased DL tolerability.</p