Distribution, growth, and transport of larval fishes and implications for population dynamics

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution February 2021.The early life stages of marine fishes play a critical role in population dynamics, largely due to their high abundance, high mortality, and ease of transport in ocean currents. This dissertation demonstrates the value of combining larval data, collected in the field and the laboratory, with model simulations. In Chapter 2, analyses of field observations of ontogenetic vertical distributions of coral reef fish revealed a diversity of behaviors both between and within families. In Caribbean-wide particle-tracking simulations of representative behaviors, surface-dwelling larvae were generally transported longer distances with greater population connectivity amongst habitat patches, while the evenly-distributed vertical behavior and downward ontogenetic vertical migration were similar to one another and led to greater retention near natal sites. However, hydrodynamics and habitat vailability created some local patterns that contradicted the overall expectation. Chapter 3 presents evidence of tuna spawning inside a large no-take marine protected area, the Phoenix Islands Protected Area (PIPA). Despite variation in temperature and chlorophyll, the larval tuna distributions were similar amongst years, with skipjack (Katsuwonus pelamis) and Thunnus spp. tunas observed in all three years. Backtracking simulations indicated that spawning occurred inside PIPA in all 3 study years, demonstrating that PIPA is protecting viable tuna spawning habitat. In Chapter 4, several lines of larval evidence support the classification of the Slope Sea as a major spawning ground for Atlantic bluefin tuna with conditions suitable for larval growth. The abundance of bluefin tuna larvae observed in the Slope Sea aligns with typical observations on the other two spawning grounds. Age and growth analyses of bluefin tuna larvae collected in the Slope Sea and the Gulf of Mexico in 2016 did not show a growth rate difference between regions, but did suggest that Slope Sea larvae are larger at the onset of exogenous feeding. Collected larvae were backtracked to locations north of Cape Hatteras and forward tracked to show that they would have been retained within the Slope Sea until the onset of swimming. As a whole, this thesis presents valuable contributions to the study of larval fishes and the attendant implications for marine resource management.National Science Foundation Graduate Research Fellowship Program (to C.M.H.), the Woods Hole Oceanographic Institution Ocean Life Institute (Grant 22569.01 to J. Llopiz and C.M.H.), the Adelaide and Charles Link Foundation, the Phoenix Islands Protected Area Trust, the J. Seward Johnson Endowment in support of the Woods Hole Oceanographic Institution's Marine Policy Center, and the WHOI Academic Programs Office

Sorption of Cr(III) and Cr(VI) to High and Low Pressure Synthetic Nano-Magnetite (Fe3O4)Particles

The binding of Cr(III) and Cr(VI) to synthetic nano-magnetie particles synthesized under open vessel conditions and a microwave assisted hydrothermal synthesis techniques was investigated. Batch studies showed that the binding of both the Cr(III) and Cr(VI) bound to the nano-materials in a pH dependent manner. The Cr(III) maximized at binding at pH 4 and 100% binding. Similarly, the Cr(VI) ions showed a maximum binding of 100% at pH 4. The data from the time dependency studies showed for the most part the majority of the binding occurred within the first 5 minutes of contact with the nanomaterial and remained constant thereafter. In addition, the effects of the possible interferences were investigated which showed some effects on the binding of both Cr(III) and Cr(VI). However, the interferences never completely eliminated the chromium binding. Isotherm studies conducted at room temperature showed the microwave synthesized nanomaterials had a binding capacity of 1208 ± 43.9 mg/g and 555 ± 10.5 mg/g for Cr(VI) and Cr(III), respectively. However, the microwave assisted synthesized nanomaterials had capacities of 1705 ± 14.5 and 555± 10.5 mg/g for Cr(VI) and Cr(III), respectively. XANES studies showed the Cr(VI) was reduced to Cr(III), and the Cr(III) remained as Cr(III). In addition, the XANES studies indicated that the chromium remained coordinated in an octahedral arrangement of oxygen atoms

Exploring interannual variability in potential spawning habitat for Atlantic bluefin tuna in the Slope Sea

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Rypina, I. I., Dotzel, M. M., Pratt, L. J., Hernandez, C. M., & Llopiz, J. K. Exploring interannual variability in potential spawning habitat for Atlantic bluefin tuna in the Slope Sea. Progress in Oceanography, 192, (2021): 102514, https://doi.org/10.1016/j.pocean.2021.102514.The Slope Sea in the Northwest Atlantic Ocean, located between the Gulf Stream and the continental shelf of the Northeast United States, is a recently-documented possible major spawning ground for Atlantic bluefin tuna (Thunnus thynnus). Larval surveys and a habitat modeling study have shown that suitable spawning habitat occurs in the Slope Sea, but the degree to which this habitat varies interannually is an open question. Here, we perform a decade-long (2009–2018) numerical modeling analysis, with simulated larvae released uniformly throughout the Slope Sea, to investigate the interannual variability in the water temperature and circulation criteria deemed necessary for successful spawning. We also quantify the influence of Gulf Stream meanders and overshoot events on larval retention and their effect on habitat suitability rates throughout the Slope Sea, defined as the percentage of simulated larvae released at a given location that satisfy criteria related to water temperature and retention near nursery habitat. Average environmental oceanographic conditions over the decade are most favorable in the western part of the Slope Sea, specifically in the Slope Gyre and away from the immediate vicinity of the Gulf Stream. Variability in domain- and summertime-averaged yearly spawning habitat suitability rates is up to 25% of the mean decadal-averaged values. Yearly habitat suitability correlates strongly with the Gulf Stream overshoot but does not correlate well with other oceanographic variables or indices, so an overshoot index can be used as a sole oceanographic proxy for predicting yearly bluefin spawning habitat suitability in the Slope Sea. Selective spawning can weaken the correlation between habitat suitability and Gulf Stream overshoot. Effort should be put towards collecting observational data against which we could validate our findings.This work was funded by a US National Science Foundation (NSF) grant (OCE-1558806) awarded to IIR, LJP, and JKL. MMD was supported by an NSF Graduate Research Fellowship. CMH was partially supported by the Adelaide and Charles Link Foundation and the J. Seward Johnson Endowment in support of the Woods Hole Oceanographic Institution’s Marine Policy Center

Identification of therapeutic targets applicable to clinical strategies in ovarian cancer

BACKGROUND: shRNA-mediated lethality screening is a useful tool to identify essential targets in cancer biology. Ovarian cancer (OC) is extremely heterogeneous and most cases are advanced stages at diagnosis. OC has a high response rate initially, but becomes resistant to standard chemotherapy. We previously employed high throughput global shRNA sensitization screens to identify NF-kB related pathways. Here, we re-analyzed our previous shRNA screens in an unbiased manner to identify clinically applicable molecular targets. METHODS: We proceeded with siRNA lethality screening using the top 55 genes in an expanded set of 6 OC cell lines. We investigated clinical relevance of candidate targets in The Cancer Genome Atlas OC dataset. To move these findings towards the clinic, we chose four pharmacological inhibitors to recapitulate the top siRNA effects: Oxozeaenol (for MAP3K7/TAK1), BI6727 (PLK1), MK1775 (WEE1), and Lapatinib (ERBB2). Cytotoxic effects were measured by cellular viability assay, as single agents and in 2-way combinations. Co-treatments were evaluated in either sequential or simultaneous exposure to drug for short term and extended periods to simulate different treatment strategies. RESULTS: Loss-of-function shRNA screens followed by short-term siRNA validation screens identified therapeutic targets in OC cells. Candidate genes were dysregulated in a subset of TCGA OCs although the alterations of these genes showed no statistical significance to overall survival. Pharmacological inhibitors such as Oxozeaenol, BI6727, and MK1775 showed cytotoxic effects in OC cells regardless of cisplatin responsiveness, while all OC cells tested were cytostatic to Lapatinib. Co-treatment with BI6727 and MK1775 at sub-lethal concentrations was equally potent to BI6727 alone at lethal concentrations without cellular re-growth after the drugs were washed off, suggesting the co-inhibition at reduced dosages may be more efficacious than maximal single-agent cytotoxic concentrations. CONCLUSIONS: Loss-of-function screen followed by in vitro target validation using chemical inhibitors identified clinically relevant targets. This approach has the potential to systematically refine therapeutic strategies in OC. These molecular target-driven strategies may provide additional therapeutic options for women whose tumors have become refractory to standard chemotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2675-5) contains supplementary material, which is available to authorized users

Sorption kinetic study of selenite and selenate onto a high and low pressure aged iron oxide nanomaterial

The sorption of selenite (SeO32−) and selenate (SeO42−) onto Fe3O4 nanomaterials produced by non microwave-assisted or microwave-assisted synthetic techniques was investigated through use of the batch technique. The phase of both synthetic nanomaterials was determined to be magnetite by X-ray diffraction. The average grain sizes of non microwave-assisted and microwave-assisted synthetic Fe3O4 were determined to be 27 and 25 nm, respectively through use of the Scherrer\u27s equation. Sorption of selenite was pH independent in the pH range of 2-6, while sorption of selenate decreased at pH 5 and 6. The addition of Cl− had no significant effect on selenite or selenate binding, while the addition of NO3− only affected selenate binding to the microwave assisted Fe3O4. A decrease of selenate binding to both synthetic particles was observed after the addition of SO42− while selenite binding was not affected. The addition of PO43− beginning at concentrations of 0.1 ppm had the most prominent effect on the binding of both selenite and selenate. The capacities of binding, determined through the use of Langmuir isotherm, were found to be 1923 and 1428 mg Se/kg of non microwave-assisted Fe3O4 and 2380 and 2369 mg Se/kg of microwave-assisted Fe3O4 for selenite and selenate, respectively

Risk of spontaneous abortion and other pregnancy outcomes in 15–25 year old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom

AbstractBackgroundWe assessed the risk of spontaneous abortion (SA) after inadvertent exposure to HPV-16/18-vaccine during pregnancy using an observational cohort design.MethodsThe study population included women aged 15–25 years registered with the Clinical Practice Research Datalink General Practice OnLine Database in the United Kingdom (UK), who received at least one HPV-16/18-vaccine dose between 1st September 2008 and 30th June 2011. Exposed women had the first day of gestation between 30 days before and 45 days (90 days for the extended exposure period) after any HPV-16/18-vaccine dose. Non-exposed women had the first day of gestation 120 days–18 months after the last dose. SA defined as foetal loss between weeks 1 and 23 of gestation (UK definition).ResultsThe frequency of SA was 11.6% (among 207 exposed) and 9.0% (632 non-exposed), women: hazard ratio (HR) adjusted for age at first day of gestation 1.30 (95% confidence interval: 0.79–2.12). Sensitivity analysis per number of doses administered (−30 to +45-day risk period) showed a HR for SA of 1.11 (0.64–1.91) for 18/178 women with one dose during the risk period versus 2.55 (1.09–5.93) in 6/29 women with two doses within a 4–5 weeks period. The proportion of pre-term/full-term/postterm deliveries, small/large for gestational age infants, and birth defects was not significantly different between exposed and non-exposed women. Results were consistent using a (United States) SA definition of foetal loss between weeks 1–19 and/or the extended risk period.ConclusionThere was no evidence of an increased risk of SA and other adverse pregnancy outcomes in young women inadvertently HPV-16/18-vaccinated around gestation. Nevertheless, women who are pregnant or trying to become pregnant are advised to postpone vaccination until completion of pregnancy

Combinatorial immunotherapies overcome MYC-driven immune evasion in triple negative breast cancer

Few patients with triple negative breast cancer (TNBC) benefit from immune checkpoint inhibitors with complete and durable remissions being quite rare. Oncogenes can regulate tumor immune infiltration, however whether oncogenes dictate diminished response to immunotherapy and whether these effects are reversible remains poorly understood. Here, we report that TNBCs with elevated MYC expression are resistant to immune checkpoint inhibitor therapy. Using mouse models and patient data, we show that MYC signaling is associated with low tumor cell PD-L1, low overall immune cell infiltration, and low tumor cell MHC-I expression. Restoring interferon signaling in the tumor increases MHC-I expression. By combining a TLR9 agonist and an agonistic antibody against OX40 with anti-PD-L1, mice experience tumor regression and are protected from new TNBC tumor outgrowth. Our findings demonstrate that MYC-dependent immune evasion is reversible and druggable, and when strategically targeted, may improve outcomes for patients treated with immune checkpoint inhibitors. The oncoprotein c-Myc is often overexpressed in triple negative breast cancer and has a role in tumor progression and resistance to therapy. Here the authors show that elevated MYC expression is correlated with low immune infiltration, diminished MHC-I pathway expression and that CpG/aOX40 treatment could overcome resistance to PD-L1 blockade in MYC-high breast tumors.Peer reviewe

CSI: Dognapping workshop : an outreach experiment designed to produce students that are hooked on science.

The CSI: Dognapping Workshop is a culmination of the more than 65 Sandian staff and intern volunteers dedication to exciting and encouraging the next generation of scientific leaders. This 2 hour workshop used a 'theatrical play' and 'hands on' activities that was fun, exciting and challenging for 3rd-5th graders while meeting science curriculum standards. In addition, new pedagogical methods were developed in order to introduce nanotechnology to the public. Survey analysis indicated that the workshop had an overall improvement and positive impact on helping the students to understand concepts from materials science and chemistry as well as increased our interaction with the K-5 community. Anecdotal analyses showed that this simple exercise will have far reaching impact with the results necessary to maintain the United States as the scientific leader in the world. This experience led to the initiation of over 100 Official Junior Scientists

Comparing the effect of a decision aid plus patient navigation with usual care on colorectal cancer screening completion in vulnerable populations: study protocol for a randomized controlled trial

Screening can reduce colorectal cancer (CRC) incidence and mortality. However, screening is underutilized in vulnerable patient populations, particularly among Latinos. Patient-directed decision aids can increase CRC screening knowledge, self-efficacy, and intent; however, their effect on actual screening test completion tends to be modest. This is probably because decision aids do not address some of the patient-specific barriers that prevent successful completion of CRC screening in these populations. These individual barriers might be addressed though patient navigation interventions. This study will test a combined decision aid and patient navigator intervention on screening completion in diverse populations of vulnerable primary care patients. We will conduct a multisite, randomized controlled trial with patient-level randomization. Planned enrollment is 300 patients aged 50 to 75 years at average CRC risk presenting for appointments at two primary clinics in North Carolina and New Mexico. Intervention participants will view a video decision aid immediately before the clinic visit. The 14 to 16 minute video presents information about fecal occult blood tests and colonoscopy and will be viewed on a portable computer tablet in English or Spanish. Clinic-based patient navigators are bilingual and bicultural and will provide both face-to-face and telephone-based navigation. Control participants will view an unrelated food safety video and receive usual care. The primary outcome is completion of a CRC screening test at six months. Planned subgroup analyses include examining intervention effectiveness in Latinos, who will be oversampled. Secondarily, the trial will evaluate the intervention effects on knowledge of CRC screening, self-efficacy, intent, and patient-provider communication. The study will also examine whether patient ethnicity, acculturation, language preference, or health insurance status moderate the intervention effect on CRC screening. This pragmatic randomized controlled trial will test a combined decision aid and patient navigator intervention targeting CRC screening completion. Findings from this trial may inform future interventions and implementation policies designed to promote CRC screening in vulnerable patient populations and to reduce screening disparities.https://doi.org/10.1186/1745-6215-15-27

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation