IFPA meeting 2016 workshop report I: Genomic communication, bioinformatics, trophoblast biology and transport systems

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2016 there were twelve themed workshops, four of which are summarized in this report. These workshops covered innovative technologies applied to new and traditional areas of placental research: 1) genomic communication; 2) bioinformatics; 3) trophoblast biology and pathology; 4) placental transport systems

Using plant volatile traps to estimate the diversity of natural enemy communities in orchard ecosystems

In this study we used sticky traps baited with plant volatile lures to monitor the biodiversity of natural enemies in orchard ecosystems in the western U.S. We compared the diversity of predator genera from season total trap catches in 37 different orchards (apple, cherry, pear and walnut) over a two-year period (2010−2011) using standardized Hill number biodiversity indices and community similarity profiles. For a subset of 23 of these orchards we were also able to monitor the change in biodiversity of predator genera over the full growing season in the different orchard crops. A total of 37,854 individuals from 31 different genera of foliage-active generalist predators were collected from all orchards combined. Mean sample coverage was high (0.98) and richness, diversity and evenness differed between crops in 2010, but not in 2011. There was more than 90% similarity in the richness of predator genera among crops and among orchards within crops, but a greater level of differentiation was observed among orchards when variation in their relative abundance and dominance in the communities was taken into account. There was a consistent rise in predator generic richness and diversity through the season in both years for apple, cherry and pear orchards, but in walnut orchards, a steep rise from March to May was followed by a decline through the rest of the season. In an additional component of the study, the species level similarity of predator and parasitoid communities was analyzed for total season trap catch data from six walnut orchards. The rarefied species richness of parasitoids was much greater than that for predators, although the diversity, evenness and dominance of the parasitoid species varied considerably among orchards. The results from this study highlight the fact that natural enemy communities in orchard ecosystems can be effectively monitored using plant volatile traps, and that these communities are surprisingly diverse despite frequent disturbance from pest management intervention

Space Flight Qualification on a Multi-Fiber Ribbon Cable and Array Connector Assembly

NASA's Goddard Space Flight Center (GSFC) cooperatively with Sandia National Laboratories completed a series of tests on three separate configurations of multi-fiber ribbon cable and MTP connector assemblies. These tests simulate the aging process of components during launch and long-term space environmental exposure. The multi-fiber ribbon cable assembly was constructed of non-outgassing materials, with radiation-hardened, graded index 100/140-micron optical fiber. The results of this characterization presented here include vibration testing, thermal vacuum monitoring, and extended radiation exposure testing data

Genome wide profiling of human embryonic stem cells (hESCs), their derivatives and embryonal carcinoma cells to develop base profiles of U.S. Federal government approved hESC lines

BACKGROUND: In order to compare the gene expression profiles of human embryonic stem cell (hESC) lines and their differentiated progeny and to monitor feeder contaminations, we have examined gene expression in seven hESC lines and human fibroblast feeder cells using Illumina(® )bead arrays that contain probes for 24,131 transcript probes. RESULTS: A total of 48 different samples (including duplicates) grown in multiple laboratories under different conditions were analyzed and pairwise comparisons were performed in all groups. Hierarchical clustering showed that blinded duplicates were correctly identified as the closest related samples. hESC lines clustered together irrespective of the laboratory in which they were maintained. hESCs could be readily distinguished from embryoid bodies (EB) differentiated from them and the karyotypically abnormal hESC line BG01V. The embryonal carcinoma (EC) line NTera2 is a useful model for evaluating characteristics of hESCs. Expression of subsets of individual genes was validated by comparing with published databases, MPSS (Massively Parallel Signature Sequencing) libraries, and parallel analysis by microarray and RT-PCR. CONCLUSION: we show that Illumina's bead array platform is a reliable, reproducible and robust method for developing base global profiles of cells and identifying similarities and differences in large number of samples

Serological evidence of a pararubulavirus and a betacoronavirus in the geographically isolated Christmas Island flying-fox (Pteropus natalis)

Due to their geographical isolation and small populations, insular bats may not be able to maintain acute immunizing viruses that rely on a large population for viral maintenance. Instead, endemic transmission may rely on viruses establishing persistent infections within hosts or inducing only short-lived neutralizing immunity. Therefore, studies on insular populations are valuable for developing broader understanding of viral maintenance in bats. The Christmas Island flying-fox (CIFF; Pteropus natalis) is endemic on Christmas Island, a remote Australian territory, and is an ideal model species to understand viral maintenance in small, geographically isolated bat populations. Serum or plasma (n = 190), oral swabs (n = 199), faeces (n = 31), urine (n = 32) and urine swabs (n = 25) were collected from 228 CIFFs. Samples were tested using multiplex serological and molecular assays, and attempts at virus isolation to determine the presence of paramyxoviruses, betacoronaviruses and Australian bat lyssavirus. Analysis of serological data provides evidence that the species is maintaining a pararubulavirus and a betacoronavirus. There was little serological evidence supporting the presence of active circulation of the other viruses assessed in the present study. No viral nucleic acid was detected and no viruses were isolated. Age-seropositivity results support the hypothesis that geographically isolated bat populations can maintain some paramyxoviruses and coronaviruses. Further studies are required to elucidate infection dynamics and characterize viruses in the CIFF. Lastly, apparent absence of some pathogens could have implications for the conservation of the CIFF if a novel disease were introduced into the population through human carriage or an invasive species. Adopting increased biosecurity protocols for ships porting on Christmas Island and for researchers and bat carers working with flying-foxes are recommended to decrease the risk of pathogen introduction and contribute to the health and conservation of the species

LCL161 enhances expansion and survival of engineered anti-tumor T cells but is restricted by death signaling

BackgroundThe genesis of SMAC mimetic drugs is founded on the observation that many cancers amplify IAP proteins to facilitate their survival, and therefore removal of these pathways would re-sensitize the cells towards apoptosis. It has become increasingly clear that SMAC mimetics also interface with the immune system in a modulatory manner. Suppression of IAP function by SMAC mimetics activates the non-canonical NF-κB pathway which can augment T cell function, opening the possibility of using SMAC mimetics to enhance immunotherapeutics.MethodsWe have investigated the SMAC mimetic LCL161, which promotes degradation of cIAP-1 and cIAP-2, as an agent for delivering transient costimulation to engineered BMCA-specific human TAC T cells. In doing so we also sought to understand the cellular and molecular effects of LCL161 on T cell biology.ResultsLCL161 activated the non-canonical NF-κB pathway and enhanced antigen-driven TAC T cell proliferation and survival. Transcriptional profiling from TAC T cells treated with LCL161 revealed differential expression of costimulatory and apoptosis-related proteins, namely CD30 and FAIM3. We hypothesized that regulation of these genes by LCL161 may influence the drug’s effects on T cells. We reversed the differential expression through genetic engineering and observed impaired costimulation by LCL161, particularly when CD30 was deleted. While LCL161 can provide a costimulatory signal to TAC T cells following exposure to isolated antigen, we did not observe a similar pattern when TAC T cells were stimulated with myeloma cells expressing the target antigen. We questioned whether FasL expression by myeloma cells may antagonize the costimulatory effects of LCL161. Fas-KO TAC T cells displayed superior expansion following antigen stimulation in the presence of LCL161, suggesting a role for Fas-related T cell death in limiting the magnitude of the T cell response to antigen in the presence of LCL161.ConclusionsOur results demonstrate that LCL161 provides costimulation to TAC T cells exposed to antigen alone, however LCL161 did not enhance TAC T cell anti-tumor function when challenged with myeloma cells and may be limited due to sensitization of T cells towards Fas-mediated apoptosis

Ship-based contributions to global ocean, weather, and climate observing systems

The role ships play in atmospheric, oceanic, and biogeochemical observations is described with a focus on measurements made within 100 m of the ocean surface. Ships include merchant and research vessels, cruise liners and ferries, fishing vessels, coast guard, military, and other government-operated ships, yachts, and a growing fleet of automated surface vessels. The present capabilities of ships to measure essential climate/ocean variables and the requirements from a broad community to address operational, commercial, and scientific needs are described. Following the guidance from the OceanObs'19 organizing committee, the authors provide a vision to expand observations needed from ships to understand and forecast the exchanges across the ocean-atmosphere interface. The vision addresses (1) recruiting vessels to improve both spatial and temporal sampling, (2) conducting multi-variate sampling on ships, (3) raising technology readiness levels of automated shipboard sensors and ship-to-shore data communications, (4) advancing quality evaluation of observations, and (5) developing a unified data management approach for observations and metadata that meets the needs of a diverse user community. Recommendations are made focusing on integrating private and autonomous vessels into the observing system, investing in sensor and communications technology development, developing an integrated data management structure that includes all types of ships, and moving towards a quality evaluation process that will result in a subset of ships being defined as mobile reference ships that will support climate studies. We envision a future where commercial, research, and privately-owned vessels are making multivariate observations using a combination of automated and human-observed measurements. All data and metadata will be documented, tracked, evaluated, distributed, and archived to benefit users of marine data. This vision looks at ships as a holistic network, not a set of disparate commercial, research, and/or third-party activities working in isolation, to bring these communities together for the mutual benefit of all

Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo–derived senescence signature (SenSig) using a foreign body response–driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type–specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34–CSF1R–TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.</p

Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo–derived senescence signature (SenSig) using a foreign body response–driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type–specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34–CSF1R–TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.</p

Transfer learning in a biomaterial fibrosis model identifies in vivo senescence heterogeneity and contributions to vascularization and matrix production across species and diverse pathologies

Cellular senescence is a state of permanent growth arrest that plays an important role in wound healing, tissue fibrosis, and tumor suppression. Despite senescent cells’ (SnCs) pathological role and therapeutic interest, their phenotype in vivo remains poorly defined. Here, we developed an in vivo–derived senescence signature (SenSig) using a foreign body response–driven fibrosis model in a p16-CreERT2;Ai14 reporter mouse. We identified pericytes and “cartilage-like” fibroblasts as senescent and defined cell type–specific senescence-associated secretory phenotypes (SASPs). Transfer learning and senescence scoring identified these two SnC populations along with endothelial and epithelial SnCs in new and publicly available murine and human data single-cell RNA sequencing (scRNAseq) datasets from diverse pathologies. Signaling analysis uncovered crosstalk between SnCs and myeloid cells via an IL34–CSF1R–TGFβR signaling axis, contributing to tissue balance of vascularization and matrix production. Overall, our study provides a senescence signature and a computational approach that may be broadly applied to identify SnC transcriptional profiles and SASP factors in wound healing, aging, and other pathologies.</p