Inhibition of autophagy impairs tumor cell invasion in an organotypic model

Autophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. It contributes to energy and organelle homeostasis and the preservation of proteome and genome integrity. Although a role in cancer is unquestionable, there are conflicting reports that autophagy can be both oncogenic and tumor suppressive, perhaps indicating that autophagy has different roles at different stages of tumor development. In this report, we address the role of autophagy in a critical stage of cancer progression—tumor cell invasion. Using a glioma cell line containing an inducible shRNA that targets the essential autophagy gene Atg12, we show that autophagy inhibition does not affect cell viability, proliferation or migration but significantly reduces cellular invasion in a 3D organotypic model. These data indicate that autophagy may play a critical role in the benign to malignant transition that is also central to the initiation of metastasis

Exposure Assessment in the National Children’s Study: Introduction

The science of exposure assessment is relatively new and evolving rapidly with the advancement of sophisticated methods for specific measurements at the picogram per gram level or lower in a variety of environmental and biologic matrices. Without this measurement capability, environmental health studies rely on questionnaires or other indirect means as the primary method to assess individual exposures. Although we use indirect methods, they are seldom used as stand-alone tools. Analyses of environmental and biologic samples have allowed us to get more precise data on exposure pathways, from sources to concentrations, to routes, to exposure, to doses. They also often allow a better estimation of the absorbed dose and its relation to potential adverse health outcomes in individuals and in populations. Here, we make note of various environmental agents and how best to assess exposure to them in the National Children’s Study—a longitudinal epidemiologic study of children’s health. Criteria for the analytical method of choice are discussed with particular emphasis on the need for long-term quality control and quality assurance measures

The Terminal A Domain of the Fibrillar Accumulation-Associated Protein (Aap) of Staphylococcus epidermidis Mediates Adhesion to Human Corneocytes▿

The opportunistic pathogen Staphylococcus epidermidis colonizes indwelling medical devices by biofilm formation but is primarily a skin resident. In many S. epidermidis strains biofilm formation is mediated by a cell wall-anchored protein, the accumulation-associated protein (Aap). Here, we investigate the role of Aap in skin adhesion. Aap is an LPXTG protein with a domain architecture including a terminal A domain and a B-repeat region. S. epidermidis NCTC 11047 expresses Aap as localized, lateral tufts of fibrils on one subpopulation of cells (Fib+), whereas a second subpopulation does not express these fibrils of Aap (Fib−). Flow cytometry showed that 72% of NCTC 11047 cells expressed Aap and that 28% of cells did not. Aap is involved in the adhesion of Fib+ cells to squamous epithelial cells from the hand (corneocytes), as the recombinant A-domain protein partially blocked binding to corneocytes. To confirm the role of the Aap A domain in corneocyte attachment, Aap was expressed on the surface of Lactococcus lactis MG1363 as sparsely distributed, peritrichous fibrils. The expression of Aap increased corneocyte adhesion 20-fold compared to L. lactis carrying Aap without an A domain. S. epidermidis isolates from catheters, artificial joints, skin, and the nose also used the A domain of Aap to adhere to corneocytes, emphasizing the role of Aap in skin adhesion. In addition, L. lactis expressing Aap with different numbers of B repeats revealed a positive correlation between the number of B repeats and adhesion to corneocytes, suggesting an additional function for the B region in enhancing A-domain-dependent attachment to skin. Therefore, in addition to its established role in biofilm formation, Aap can also promote adhesion to corneocytes and is likely to be an important adhesin in S. epidermidis skin colonization

The lower bathyal and abyssal seafloor fauna of eastern Australia

Background Our knowledge of the benthic fauna at lower bathyal to abyssal (LBA, > 2000 m) depths off Eastern Australia was very limited with only a few samples having been collected from these habitats over the last 150 years. In May–June 2017, the IN2017_V03 expedition of the RV Investigator sampled LBA benthic communities along the lower slope and abyss of Australia’s eastern margin from off mid-Tasmania (42°S) to the Coral Sea (23°S), with particular emphasis on describing and analysing patterns of biodiversity that occur within a newly declared network of offshore marine parks. Methods The study design was to deploy a 4 m (metal) beam trawl and Brenke sled to collect samples on soft sediment substrata at the target seafloor depths of 2500 and 4000 m at every 1.5 degrees of latitude along the western boundary of the Tasman Sea from 42° to 23°S, traversing seven Australian Marine Parks. Results The biological sampling included 35 beam trawls, 28 Brenke sleds, 8 box cores, 20 surface meso-zooplankton tows, and 7 Deep Towed Camera transects. In total, 25,710 specimens were identified to 1084 taxonomic entities, including 847 species-level, 144 genus-level and 69 family-level and 24 higher-level taxa. Of the species-level taxa, only 457 were assigned species-level taxonomic names, which implies that up to 58% of the collected fauna is undescribed. In addition, the ranges of numerous species have been extended to include the western Tasman Sea. Conclusions The lower bathyal and abyssal fauna of soft sediment seafloors off eastern Australia has been systematically surveyed for the first time. The resultant collections will provide the foundation for much future ecological, biogeographical, phylogenetic and taxonomic research