In order to identify the earliest genetic changes that precipitate species formation, it is useful to study genetic incompatibilities that cause only mild dysfunction when incompatible alleles are combined in an interpopulation hybrid. Such hybridization within the nematode species Caenorhabditis briggsae has been suggested to result in selection against certain combinations of nuclear and mitochondrial alleles, raising the possibility that mitochondrial–nuclear (mitonuclear) epistasis reduces hybrid fitness. To test this hypothesis, cytoplasmic–nuclear hybrids (cybrids) were created to purposefully disrupt any epistatic interactions. Experimental analysis of the cybrids suggests that mitonuclear discord can result in decreased fecundity, increased lipid content, and increased mitochondrial reactive oxygen species levels. Many of these effects were asymmetric with respect to cross direction, as expected if cytoplasmic–nuclear Dobzhansky-Muller incompatibilities exist. One such effect is consistent with the interpretation that disrupting coevolved mitochondrial and nuclear loci impacts mitochondrial function and organismal fitness. These findings enhance efforts to study the genesis, identity, and maintenance of genetic incompatibilities that precipitate the speciation process.

BackgroundNanoparticles can be used for targeted drug delivery, in particular for brain cancer therapy. However, this requires a detailed analysis of nanoparticles from the associated microvasculature to the tumor, not easy because of the required high spatial resolution. The objective of this study is to demonstrate an experimental solution of this problem, based in vivo and post-mortem whole organ imaging plus nanoscale 3-dimensional (3D) X-ray microscopy.ResultsThe use of gold nanoparticles (AuNPs) as contrast agents paved the way to a detailed high-resolution three dimensional (3D) X-ray and fluorescence imaging analysis of the relation between xenografted glioma cells and the tumor-induced angiogenic microvasculature. The images of the angiogenic microvessels revealed nanoparticle leakage. Complementary tests showed that after endocytotic internalization fluorescent AuNPs allow the visible-light detection of cells.ConclusionsAuNP-loading of cells could be extended from the case presented here to other imaging techniques. In our study, they enabled us to (1) identify primary glioma cells at inoculation sites in mice brains; (2) follow the subsequent development of gliomas. (3) Detect the full details of the tumor-related microvasculature; (4) Finding leakage of AuNPs from the tumor-related vasculature, in contrast to no leakage from normal vasculature.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-015-0140-2) contains supplementary material, which is available to authorized users.

Purpose To investigate the ocular surface microbiome of patients with unilateral or asymmetric glaucoma being treated with topical ophthalmic medications in one eye and to determine whether microbial community changes were related to measures of ocular surface disease. Methods V3-V4 16S rRNA sequencing was conducted on ocular surface swabs collected from both eyes of 17 subjects: 10 patients with asymmetric/unilateral glaucoma using topical glaucoma therapy on only one eye and seven age-matched, healthy controls with no history of ocular disease or eyedrop use. Samples were categorized into three groups: patients’ glaucomatous eye treated with eyedrops, patients’ contralateral eye without eyedrops, and healthy control eyes. Comparisons were made for microbial diversity and composition, with differences in composition tested for association with ocular surface disease measures including tear meniscus height, tear break-up time, and Dry Eye Questionnaire. Results Samples obtained from the patients’ treated and untreated eyes both had significantly greater alpha-diversity and relative abundance of gram-negative organisms compared to healthy controls. The microbial composition of patient eyes was associated with decreased tear meniscus height and tear break-up time, whereas metagenomic predictions, based on 16S rRNA data, suggested increased synthesis of lipopolysaccharide. Conclusions The ocular surface microbiome of patients taking unilateral preserved glaucoma drops is characterized by a highly diverse array of gram-negative bacteria that is significantly different from the predominantly gram-positive microbes detected on healthy control eyes. These compositional differences were associated with decreased tear film measures and distinct inferred protein synthesis pathways, suggesting a potential link between microbial alterations and ocular surface inflammation.

Rationale and Objectives Low dose chest computed tomography (LDCT), increasingly being used for screening of lung cancer, may also be used to measure breast density, which is proven as a risk factor for breast cancer. In this study we developed a segmentation method to measure quantitative breast density on CT images and correlated with MR density. Materials and Methods Forty healthy females receiving both LDCT and breast magnetic resonance imaging (MRI) were studied. A semi-automatic method was applied to quantify the breast density on LDCT images. The intra-, inter-operator reproducibility was evaluated. The volumetric density on MRI was obtained by using a well-established automatic template-based segmentation method. The breast volume (BV), fibroglandular tissue volume (FV), and percent breast density (PD) measured on LDCT and MRI were compared. Results The measurements of BV, FV, and PD on LDCT images yields highly consistent results, with the intraclass correlation coefficient (ICC) of 0.999 for BV, 0.977 for FV, and 0.966 for PD for intra-operator reproducibility; and ICC of 0.953 for BV, 0.974 for FV, and 0.973 for PD for inter-operator reproducibility. The BV, FV, and PD measured on LDCT and MRI were well correlated (all r≥0.90). Bland-Altman plots showed that a larger BV and FV were measured on LDCT compared with MRI. Conclusions The preliminary results showed that quantitative breast density can be measured from LDCT, and that our segmentation method could yield a high reproducibility on the measured volume and percent breast density. The results measured on LDCT and MRI were highly correlated. Our results showed that LDCT may provide valuable information about breast density for evaluating breast cancer risk.

Purpose of reviewCurrent literature describing the ocular surface microbiome and host immunity are reviewed alongside experiments studying perturbations of the microbiome to explore the hypothesis that disruption of a healthy microbiome may predispose the ocular surface to inflammation and infection.Recent findingsThe ocular surface of healthy subjects is colonized by stable, pauci-microbial communities that are tolerant to the host immune response and are dominated by the genera Corynebacterium, Propionibacterium, and Staphylococcus. In animal studies, commensal microbes on the ocular surface interact with toll-like receptors to regulate the immune system through immune cell and inflammatory cytokine production, promoting homeostasis and protecting against infection. Contact lens wear, lens wash solutions, and preserved topical medications can disrupt the native microbiome and alter the relative diversity and composition of microbes on the ocular surface.SummaryThe ocular surface microbiome confers protection against pathogenic colonization and immune dysregulation. Disruption of this microbiome by exogenous factors may alter the resistance of the ocular surface to infection. Further study of the relationships between human ocular surface microbiome and the local immune response are needed.

Recognizing the MRI appearance of tumor recurrence in breast myocutaneous flap reconstructions is important for early detection of recurrence and in the evaluation of extent of disease to guide clinical management. Bilateral breast MRI for high-risk cancer screening of the native breast is a unique opportunity to detect recurrence in the reconstructed breast before it is clinically apparent. We describe a range of MRI appearances of breast cancer recurrence in patients with myocutaneous flap reconstructions.

Introduction: There are few curriculum materials designed to provide training and support for peer tutors to become effective clinical skills teachers. We designed the Clinical Skills Tutoring Program (CSTP) curriculum to guide tutors to help their students reflect on clinical skills performance, create an individualized learning plan, and engage in improvement based on feedback to achieve clinical skills competencies. Methods: Curriculum content was delivered through an in-person training session, formal curriculum written content, online resources, and longitudinal support from faculty directors. Tutors (fourth-year medical students) received surveys to evaluate the in-person training session, curriculum resources, and overall program experience. Student participants (medical students of any year) completed a survey to rate their satisfaction in working with their tutors. Results: There were 12 tutors in cohort 1 and 18 tutors in cohort 2. Survey response rates ranged from 50% to 70% among tutors. The tutors were satisfied with the in-person training session, program experience, curriculum resources, support from directors, development of learning goals with the student, and clinical skills practice with the student (mean Likert ratings greater than 4 out of 5). Student participants were satisfied with their experience creating learning goals and receiving feedback from their tutors. Discussion: The tutor curriculum fills a gap by training and supporting tutors before and during their work with students needing further resources and remediation in one or more clinical skills domains. The curriculum can be implemented and further adapted by other tutoring programs locally and nationally.

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