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Biology subjects

Neves, E.

Publications and source records attributed to Neves, E..

3 recordsLinked to original sources

The migration of an expanding sea turtle population alters the structure of marine megafauna communities

Interactions shape community structures, yet the impact of large migratory influxes on communities, particularly marine ones, remains elusive. Using drone surveys, we investigated changes of marine megafauna communities (e.g., sharks, rays), during the mass migration of loggerhead sea turtles (Caretta caretta) in Cabo Verde, one of the largest, and growing, rookeries globally and a biodiversity hotspot. In high nesting density areas, with over 6,000 turtles detected in-water at the seasons peak, the community structured with sharks distributing between the turtles and the coastline. In low-density areas ([~]500 turtles), no structuring was detected. After the seasons peak, increased shark abundance and shoreward movement suggest they anticipate a nutrient pulse from emerging hatchlings. Our results highlight the role of sea turtle abundance in structuring marine communities, both as a high-quality food resource (hatchlings) and a likely non-consumable species (adults). Overall, we show the significant impact of migratory species on marine megafauna communities.

ecology↗

Targeting glioblastoma tumor hyaluronan to enhance therapeutic interventions that regulate metabolic cell properties

Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. We aim here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling. We use tissue engineering approaches to recreate the three-dimensional tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient derived xenograft GBM cells. We reveal that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype dependent manner. We propose a tumor specific combination treatment of HYAL and HAS inhibitors to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand - dependent signaling roles of hyaluronan in glioblastoma. SignificanceThe control of aberrant hyaluronan metabolism in the tumor microenvironment can improve the efficacy of current treatments. Bioengineered preclinical models demonstrate potential to predict, stratify and accelerate the development of cancer treatments.

bioengineering↗

Patient-Derived Three-Dimensional Cortical Neurospheres to Model Parkinson's Disease

There are currently no preventive or disease-modifying therapies for Parkinsons Disease (PD). Failures in clinical trials necessitate a re-evaluation of existing pre-clinical models in order to adopt systems that better recapitulate underlying disease mechanisms and better predict clinical outcomes. In recent years, models utilizing patient-derived induced pluripotent stem cells (iPSCs) have emerged as attractive models to recapitulate disease-relevant neuropathology in vitro without exogenous overexpression of disease-related pathologic proteins. Here, we utilized iPSCs derived from patients with early-onset PD and dementia phenotypes that harbored either a point mutation (A53T) or multiplication at the -synuclein/SNCA gene locus. We generated a three-dimensional (3D) cortical neurosphere culture model to better mimic the tissue microenvironment of the brain. We extensively characterized the differentiation process using quantitative PCR, Western immunoblotting and immunofluorescence staining. Differentiation and aging of the neurospheres revealed alterations in fatty acid profiles and elevated total and pathogenic phospho--synuclein levels in both A53T and the triplication lines compared to their isogenic control lines. Furthermore, treatment of the neurospheres with a small molecule inhibitor of stearoyl CoA desaturase (SCD) attenuated the protein accumulation and aberrant fatty acid profile phenotypes. Our findings suggest that the 3D cortical neurosphere model is a useful tool to interrogate targets for PD and amenable to test small molecule therapeutics.

neuroscience↗