bioRxiv Science⌕ Search

Biology subjects

Gifford, S.

Publications and source records attributed to Gifford, S..

3 recordsLinked to original sources

Protistan plankton communities in the Galapagos Archipelago respond to changes in deep water masses resulting from the 2015/16 El Nino

The Galapagos Archipelago lies within the eastern equatorial Pacific Ocean at the convergence of major ocean currents that are subject to changes in circulation. The nutrient-rich Equatorial Undercurrent upwells from the west onto the Galapagos platform, stimulating primary production, but this source of deep water weakens during El Nino events. From measurements collected on repeat cruises, the 2015/16 El Nino was associated with declines in phytoplankton biomass at most sites throughout the archipelago and reduced utilization of nitrate, particularly in large-sized phytoplankton in the western region. Protistan assemblages were identified by sequencing the V4 region of the 18S rRNA gene. Dinoflagellates, chlorophytes, and diatoms dominated most sites. Shifts in dinoflagellate communities were most apparent between the years; parasitic dinoflagellates, Syndiniales, were highly detected during the El Nino (2015) while the dinoflagellate genus, Gyrodinium dominated many sites during the neutral period (2016). Variations in protistan communities were most strongly correlated with changes in subthermocline water density. These findings indicate that marine protistan communities in this region are regimented by deep water mass sources and thus could be profoundly affected by altered ocean circulation.

ecology↗

Unannotated small RNA clusters in circulating extracellular vesicles detect early stage liver cancer

BackgroundHepatocellular carcinoma (HCC) is among the deadliest malignancies and surveillance tools for early detection are suboptimal. Extracellular vesicles (EVs) have gained increasing scientific interest due to their involvement in tumor initiation and metastasis, however, most extracellular RNA (exRNA) biomarker studies are limited to annotated genomic regions. MethodsEVs were isolated with ultracentrifugation and nanoDLD and quality assessed by electron microscopy, immunoblotting, nanoparticle tracking, and deconvolution analysis. We performed genome-wide small exRNA sequencing, including unannotated transcripts. We identified small RNA clusters (smRCs) and delineated their key genomic features across biospecimens (blood, urine, tissue) and EV isolation techniques. A 3-smRC signature for early HCC detection was trained and validated in two independent cohorts. ResultsEV-derived smRCs were dominated by uncharacterized, unannotated small RNA and uniformly tiled across the genome with a consensus sequence of 20bp. A 3-smRC signature was significantly overexpressed in circulating EVs of HCC patients compared to controls at risk or patients with non-HCC malignancies (p<0.01, n=157). An independent validation in a phase 2 biomarker study revealed 86% sensitivity and 91% specificity for the detection of early HCC from controls at risk (i.e. cirrhosis or chronic liver disease, n=209) (positive predictive value (PPV): 89%, area under the ROC curve [AUC]: 0.87). The 3-smRC signature was independent of alpha-fetoprotein (p<0.0001) and a composite model yielded an increased AUC of 0.93 (sensitivity: 85%, specificity: 94%, PPV: 95%). ConclusionAn exRNA-based 3-smRC signature from plasma detects early stage HCC, which directly leads to the prospect of a minimally-invasive, blood-only, operator-independent surveillance biomarker. One sentence summaryWe employ a novel, data-driven approach to identify and characterize small RNA clusters from unannotated loci in extracellular vesicle-derived RNA across different cancer types, isolation techniques, and biofluids, facilitating discovery of a robust biomarker for detection of early stage liver cancer.

cancer biology↗

A model Roseobacter employs a diffusible killing mechanism to eliminate competitors

The roseobacter clade is a group of -proteobacteria that have diverse metabolic and regulatory capabilities. They are abundant in marine environments and have a substantial role in marine ecology and biogeochemistry. However, interactions between roseobacters and other bacterioplankton have not been extensively explored. In this study, we identify a killing mechanism in the model Roseobacter Ruegeria pomeroyi DSS-3 by competing it against a group of phylogenetically diverse bacteria. The killing mechanism involves an unidentified antimicrobial compound that is produced when cells are grown on both surfaces and in suspension and is dependent on cell density. A screen of random transposon mutants revealed the killing phenotype, as well as resistance to the antimicrobial, require genes within an ~8 kb putative {gamma}-butyrolactone synthesis gene cluster, which resembles similar pheromone-sensing systems in actinomycetes that regulate secondary metabolite production. Transcriptomics revealed the gene cluster is highly upregulated in wild-type DSS-3 compared to a non-killer mutant when grown in liquid coculture with a roseobacter target. Our findings show that R. pomeroyi has the capability to eliminate closely- and distantly-related competitors, providing a mechanism to alter the community structure and function in its native habitats.

microbiology↗