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Roberts, C. M.

Publications and source records attributed to Roberts, C. M..

10 recordsLinked to original sources

Ancient environmental DNA reveals the distinct fingerprints of whaling and climate change on Antarctic marine biodiversity

The Southern Ocean is a disproportionately large contributor to Earth system processes, playing a crucial role in the global transport of carbon, oxygen and heat. It also hosts enormous seasonal biological productivity that supports diverse endemic marine biodiversity. Industrial whaling in the first half of the 20th century and recent human-driven climate change have both profoundly altered Antarctic ecosystems, but ecological surveys of these impacts are limited to well-known taxa in the short period since monitoring began. Here, we analysed five sediment records to reconstruct more than two centuries of ecosystem change across the Western Antarctic Peninsula, spanning periods before and during major human impacts. Environmental DNA metabarcoding of these records revealed substantial biodiversity shifts, with change accelerating in recent decades. We find a significant role for both climate change and whaling in restructuring communities, identifying unique variance in whole-community change explained by each driver. Moreover, we find a negative association between whaling and metazoan families which feed from the water column, suggesting that pre-whaling ecosystems had greater pelagic productivity. Overall, our results reveal baseline Antarctic biodiversity from long before observational records and identify a distinct fingerprint of human drivers in this fragile, rapidly changing ecosystem.

ecology↗

Sediment depth-dependent trait expression controls species contributions to nutrient cycling

Global biodiversity loss is restructuring ecological communities and compromising ecosystem functioning. Yet, we still lack an empirical understanding of how specific trait combinations regulate ecosystem processes or how their functional expression is organised within the immediate environment. Here, we investigated trait-expression across 17 functionally contrasting sediment-dwelling marine invertebrate species. We show that while sediment reworking and burrow ventilation are depth dependent, their influence on nutrient concentrations are highly nutrient-specific. Our analyses reveal that nutrient concentrations are better explained by continuous, spatially explicit trait combinations than by categorical bioturbation modes. Surface modification was associated with higher ammonium concentrations, moderated by ventilation, while deeper sediment reworking and biomass were associated with higher nitrite concentrations. Phosphate relationships were weak, and nitrate was not explained by the measured traits. These results establish a mechanistic baseline for species-specific trait-nutrient relationships under controlled conditions. This shift from categorical trait assignments to a spatially explicit, empirically resolved trait-interaction framework provides a mechanistic foundation for predicting how changes in species composition may alter benthic nutrient cycling.

ecology↗

A Tale of Two Cell Lines: Characterization of differential efficacy of small molecule drugs cediranib and NU-7441 on primary vs. metastatic colorectal cancer

Colorectal cancer is recognized as one of the leading causes of cancer death amongst both sexes in the U.S. Despite rigorous screening, those diagnosed with colon cancer often face poor prognosis, and approximately 70% of affected patients will develop metastatic relapse. The investigation of colon carcinoma cell lines genetic variability and response to chemotherapy panels may aid in targeting therapies to improve outcomes. This study aims to find correlations between metastasis status, gene variability, and drug response. We used two cell lines that were isolated from the same 51-year-old male with colorectal adenocarcinoma: a primary tumor-derived line (SW480) and a secondary metastasis-derived line (SW620). Live cell imaging using time-lapse microscopy over three days exhibited differential cell death responses following treatment with multiple chemotherapeutic agents, particularly cediranib and Nu-7441, with SW620 demonstrating greater sensitivity. Western blots revealed changes in DNA repair machinery expression (particularly NHEJ proteins) between SW480 and SW620. RNA sequencing and Gene Ontology analysis corroborated our findings, demonstrating upregulated DNA repair and metabolic survival genes including TGM2 in SW620 and PROM1 in SW480. An SW620 line grown in non-attachment plates and then reattached (SW620F) exhibited high DNA-PKcs activation and drug sensitivity. Correlation between drug response and gene expression crucial to cell growth and successful metastasis may reveal new biomarkers to target potential treatments.

cancer biology↗

Naltrexone has variable and schedule-dependent effects on oral squamous cell carcinoma cells

Oral squamous cell carcinoma is marked by profound differences in survival between localized and disseminated disease. While at its site of origin, oral cancer is frequently treated with surgery and/or radiation, leading to approximately 70% five-year survival. In metastatic cases, chemotherapy is preferred, but drug resistance and therapy failure is common in this setting, leading to five-year survival below 40%. New therapeutic approaches are therefore needed to supplement existing chemotherapies and improve outcomes. Naltrexone, an opioid antagonist most well-known for treatment of substance abuse, has been evaluated at low doses in other contexts, including inflammation, autoimmunity, and other forms of cancer. In this study, we sought to determine if intermittent dosing of naltrexone would impact oral cancer cell survival, either as a single agent or in combination with traditional chemotherapy. We found that its effects alone were negligible, but that combination with cytotoxic drugs may have promise as a novel treatment strategy. Further study and optimization will be needed to determine if these findings will be of clinical benefit.

pharmacology and toxicology↗

Protecting seabed sediment carbon for climate mitigation: a UK case study

Protecting areas of seabed sediment would appear to be an important climate mitigation strategy, however carbon has not been considered in national management plans. Using spatial analyses we show, in the UK Exclusive Economic Zone (EEZ), high potential organic carbon loss due to mobile bottom fishing is likely to be geographically restricted. Currently designated seabed marine protected areas (MPAs) cover 32.9% of the EEZ, 30.0% of carbon stocks, but only 12.9% of fishing disturbance. If all MPAs were closed to mobile bottom fishing, we estimate a prevention of only 6.9% of potential organic carbon losses due to fishing disturbance across the EEZ. In contrast, areas identified as having largest climate change mitigation potential cover just 16.5% of the EEZ, contain 24.7% of OC stocks and closing these areas to mobile fishing could save 29.6% of potential carbon losses. We must re-evaluate current seabed management plans and incorporate evidence-based carbon considerations. TeaserRestrictions on bottom trawling and dredging outside of MPA networks may be necessary to derive a climate mitigation benefit.

ecology↗

The potential for mobile demersal fishing to reduce carbon storage and sequestration in seabed sediments

Subtidal marine sediments are one of the planets primary carbon stores and strongly influence the oceanic sink for atmospheric CO2. By far the most pervasive human activity occurring on the seabed is bottom trawling and dredging for fish and shellfish. A global first-order estimate suggested mobile demersal fishing activities may cause 160-400 Mt of organic carbon (OC) to be remineralised annually from seabed sediment carbon stores. There are, however, many uncertainties in this calculation. Here, we discuss the potential drivers of change in seabed OC stores due to mobile demersal fishing activities and conduct a systematic review, synthesising studies where this interaction has been directly investigated. Mobile demersal fishing would be expected to reduce OC in seabed stores, albeit with site-specific variability. Reductions would occur due to lower production of flora and fauna, the loss of fine flocculent material, increased sediment resuspension, mixing and transport, and increased oxygen exposure. This would be offset to some extent by reduced faunal bioturbation and respiration, increased off-shelf transport and increases in primary production from the resuspension of nutrients. Studies which directly investigated the impact of demersal fishing on OC stocks had mixed results. A finding of no significant effect was reported in 51% of 59 experimental contrasts; 41% reported lower OC due to fishing activities, with 8% reporting higher OC. In relation to remineralisation rates within the seabed, 14 experimental contrasts reported that demersal fishing activities decreased remineralisation, with four reporting higher remineralisation rates. The direction of effects was related to sediment type, impact duration, study design and local hydrography. More evidence is urgently needed to accurately quantify the impact of anthropogenic physical disturbance on seabed carbon in different environmental settings, and incorporate full evidence-based carbon considerations into global seabed management.

ecology↗

Essential Role of Placenta Derived Interferon Stimulated Gene 20 Against ZIKA Virus Infection

Zika virus is a positive-sense single-stranded RNA virus, which can be transmitted across the placenta and leads to adverse effects on fetal development during pregnancy. The severity of these complications highlights the importance of prevention and treatment. However, no vaccines or drugs are currently available. In this study, we characterized the IFN{beta}-mediated antiviral response in trophoblast cells in order to identify critical components that are necessary for the successful control of viral replication; and determined whether we could use the components of the IFN-induced response as a replacement therapy for ZIKA viral infection during pregnancy. We identified and characterized interferon stimulated gene 20 (ISG20), playing a central role in controlling Zika infection in trophoblast cells, and successfully established a recombinant ISG20-Fc protein that effectively decrease viral titers in vitro and in vivo by maintaining its exonuclease activity and displaying immune modulatory functions. Therefore, rISG20-Fc is a promising anti-viral/immune modulatory approach for the control and prevention of RNA viral infections such as ZIKA virus.

immunology↗

Amyloid beta acts synergistically as a pro-inflammatory cytokine

The amyloid beta (A{beta}) peptide is believed to play a central role in Alzheimers disease (AD), the most common age-related neurodegenerative disorder. However, the natural, evolutionarily-selected functions of A{beta} are incompletely understood. Here, we report that nanomolar concentrations of A{beta} act synergistically with known cytokines to promote pro-inflammatory activation in primary human astrocytes (a cell type increasingly implicated in brain aging and AD). Using transcriptomics (RNA-seq), we show that A{beta} can directly substitute for the complement component C1q in a cytokine cocktail previously shown to induce astrocyte immune activation. Furthermore, we show that astrocytes synergistically activated by A{beta} have a transcriptional signature similar to neurotoxic "A1" astrocytes known to accumulate with age and in AD. Interestingly, we find that this biological action of A{beta} at low concentrations is distinct from the transcriptome changes induced by the high/supraphysiological doses of A{beta} often used in in vitro studies. Collectively, our results suggest an important, cytokine-like function for A{beta} and a novel mechanism by which it may directly contribute to the neuroinflammation associated with brain aging and AD.

molecular biology↗

NON-RANDOM TIMING OF ECOLOGICAL SHIFTS ON CARIBBEAN CORAL REEFS SUGGESTS REGIONAL CAUSES OF CHANGE

AO_SCPLOWBSTRACTC_SCPLOWCaribbean reefs have experienced unprecedented changes in the past four decades. Of great concern is the perceived widespread shift from coral to macroalgal dominance and the question of whether it represents a new, stable equilibrium for coral-reef communities. The primary causes of the shift -- grazing pressure (top-down), nutrient loading (bottom-up) or direct coral mortality (side-in) -- still remain somewhat controversial in the coral reef literature. We have attempted to tease out the relative importance of each of these causes. Four insights emerge from our analysis of an early regional dataset of information on the benthic composition of Caribbean reefs spanning the years 1977-2001. First, although three-quarters of reef sites have experienced coral declines concomitant with macroalgal increases, fewer than 10% of the more than 200 sites studied were dominated by macroalgae in 2001, by even the most conservative definition of dominance. Using relative dominance as the threshold, a total of 49 coral-to-macroalgae shifts were detected. This total represents [~]35% of all sites that were dominated by coral at the start of their monitoring periods. Four shifts (8.2%) occurred because of coral loss with no change in macroalgal cover, 15 (30.6%) occurred because of macroalgal gain without coral loss, and 30 (61.2%) occurred owing to concomitant coral decline and macroalgal increase. Second, the timing of shifts at the regional scale is most consistent with the side-in model of reef degradation, which invokes coral mortality as a precursor to macroalgal takeover, because more shifts occurred after regional coral-mortality events than expected by chance. Third, instantaneous observations taken at the start and end of the time-series for individual sites showed these reefs existed along a continuum of coral and macroalgal cover. The continuous, broadly negative relationship between coral and macroalgal cover suggests that in some cases coral-to-macroalgae phase shifts may be reversed by removing sources of perturbation or restoring critical components such as the herbivorous sea urchin Diadema antillarum to the system. The five instances in which macroalgal dominance was reversed corroborate the conclusion that macroalgal dominance is not a stable, alternative community state as has been commonly assumed. Fourth, the fact that the loss in regional coral cover and concomitant changes to the benthic community are related to punctuated, discrete events with known causes (i.e. coral disease and bleaching), lends credence to the hypothesis that coral reefs of the Caribbean have been under assault from climate-change-related maladies since the 1970s.

ecology↗

Transcriptome analysis of genetically matched human induced pluripotent stem cells disomic or trisomic for chromosome 21.

Trisomy of chromosome 21, the genetic cause of Down syndrome, has the potential to alter expression of genes on chromosome 21, as well as other locations throughout the genome. These transcriptome changes are likely to underlie the Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in-depth analysis of transcriptome changes resulting from trisomy of chromosome 21, using induced pluripotent stem cells (iPSCs) derived from a single individual with Down syndrome. These cells were originally derived by Li et al, who genetically targeted chromosome 21 in trisomic iPSCs, allowing selection of disomic sibling iPSC clones. Analyses were conducted on trisomic/disomic cell pairs maintained as iPSCs or differentiated into cortical neuronal cultures. In addition to characterization of gene expression levels, we have also investigated patterns of RNA adenosine-to-inosine editing, alternative splicing, and repetitive element expression, aspects of the transcriptome that have not been significantly characterized in the context of Down syndrome. We identified significant changes in transcript accumulation associated with chromosome 21 trisomy, as well as changes in alternative splicing and repetitive element transcripts. Unexpectedly, the trisomic iPSCs we characterized expressed higher levels of neuronal transcripts than control disomic iPSCs, and readily differentiated into cortical neurons, in contrast to another reported study. Comparison of our transcriptome data with similar studies of trisomic iPSCs suggests that trisomy of chromosome 21 may not intrinsically limit neuronal differentiation, but instead may interfere with the maintenance of pluripotency.

genetics↗