Engaging at the science-policy interface as an early-career researcher: experiences and perceptions in biodiversity and ecosystem services research

Effective knowledge exchange at science-policy interfaces (SPIs) can foster evidence-informed policy-making through the integration of a wide range of knowledge inputs. This is especially crucial for conservation and sustainable use of biodiversity and ecosystem services (ES), human well-being and sustainable development. Early-career researchers (ECRs) can contribute significantly to knowledge exchange at SPIs. Recognizing that, several capacity building programs focused on sustainability have been introduced recently. However, little is known about the experiences and perceptions of ECRs in relation to SPIs. Our study focused on SPI engagement of ECRs who conduct research on biodiversity and ES, as perceived and experienced. Specifically, we addressed ‘motivations’, ‘barriers’ and ‘opportunities and ‘benefits’. A total of 145 ECRs have completed the survey. Our results showed that ECRs were generally interested to engage in SPIs and believed it to be beneficial in terms of contributing to societal change, understanding policy processes and career development. Respondents perceived lack of understanding about involvement channels, engagement opportunities, funding, training, perceived credibility of ECRs by other actors and encouragement of senior colleagues as barriers to engaging in SPIs. Those who have already participated in SPIs generally saw fewer barriers and more opportunities. A key reason for dissatisfaction with experience in SPIs was a lack of impact and uptake of science-policy outputs by policymakers–an issue that likely extends beyond ECRs and implies the need for transformations in knowledge exchange within SPIs. In conclusion, based on insights from our survey, we outline several opportunities for increased and better facilitation of ECR engagement in SPIs. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Genetic Signature of Rapid IHHNV (Infectious Hypodermal and Hematopoietic Necrosis Virus) Expansion in Wild Penaeus Shrimp Populations

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is a widely distributed single-stranded DNA parvovirus that has been responsible for major losses in wild and farmed penaeid shrimp populations on the northwestern Pacific coast of Mexico since the early 1990's. IHHNV has been considered a slow-evolving, stable virus because shrimp populations in this region have recovered to pre-epizootic levels, and limited nucleotide variation has been found in a small number of IHHNV isolates studied from this region. To gain insight into IHHNV evolutionary and population dynamics, we analyzed IHHNV capsid protein gene sequences from 89 Penaeus shrimp, along with 14 previously published sequences. Using Bayesian coalescent approaches, we calculated a mean rate of nucleotide substitution for IHHNV that was unexpectedly high (1.39×10−4 substitutions/site/year) and comparable to that reported for RNA viruses. We found more genetic diversity than previously reported for IHHNV isolates and highly significant subdivision among the viral populations in Mexican waters. Past changes in effective number of infections that we infer from Bayesian skyline plots closely correspond to IHHNV epizootiological historical records. Given the high evolutionary rate and the observed regional isolation of IHHNV in shrimp populations in the Gulf of California, we suggest regular monitoring of wild and farmed shrimp and restriction of shrimp movement as preventative measures for future viral outbreaks

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Optical imaging of tumor hypoxia dynamics

The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent∕phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique

Delivery-corrected imaging of fluorescently-labeled glucose reveals distinct metabolic phenotypes in murine breast cancer.

When monitoring response to cancer therapy, it is important to differentiate changes in glucose tracer uptake caused by altered delivery versus a true metabolic shift. Here, we propose an optical imaging method to quantify glucose uptake and correct for in vivo delivery effects. Glucose uptake was measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-D-glucose (2-NBDG) in mice implanted with dorsal skin flap window chambers. Additionally, vascular oxygenation (SO2) was calculated using only endogenous hemoglobin contrast. Results showed that the delivery factor proposed for correction, "RD", reported on red blood cell velocity and injected 2-NBDG dose. Delivery-corrected 2-NBDG uptake (2-NBDG60/RD) inversely correlated with blood glucose in normal tissue, indicating sensitivity to glucose demand. We further applied our method in metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. The ratio 2-NBDG60/RD was increased in 4T1 tumors relative to 4T07 tumors yet average SO2 was comparable, suggesting a shift toward a "Warburgian" (aerobic glycolysis) metabolism in the metastatic 4T1 line. In heterogeneous regions of both 4T1 and 4T07, 2-NBDG60/RD increased slightly but significantly as vascular oxygenation decreased, indicative of the Pasteur effect in both tumors. These data demonstrate the utility of delivery-corrected 2-NBDG and vascular oxygenation imaging for differentiating metabolic phenotypes in vivo

Delivery rate affects uptake of a fluorescent glucose analog in murine metastatic breast cancer.

We demonstrate an optical strategy using intravital microscopy of dorsal skin flap window chamber models to image glucose uptake and vascular oxygenation in vivo. Glucose uptake was imaged using a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). SO2 was imaged using the differential absorption properties of oxygenated [HbO2] and deoxygenated hemoglobin [dHb]. This study was carried out on two sibling murine mammary adenocarcinoma lines, 4T1 and 4T07. 2-NBDG uptake in the 4T1 tumors was lowest when rates of delivery and clearance were lowest, indicating perfusion-limited uptake in poorly oxygenated tumor regions. For increasing rates of delivery that were still lower than the glucose consumption rate (as measured in vitro), both 2-NBDG uptake and the clearance rate from the tumor increased. When the rate of delivery of 2-NBDG exceeded the glucose consumption rate, 2-NBDG uptake decreased with any further increase in rate of delivery, but the clearance rate continued to increase. This inflection point was not observed in the 4T07 tumors due to an absence of low delivery rates close to the glucose consumption rate. In the 4T07 tumors, 2-NBDG uptake increased with increasing rates of delivery at low rates of clearance. Our results demonstrate that 2-NBDG uptake in tumors is influenced by the rates of delivery and clearance of the tracer. The rates of delivery and clearance are, in turn, dependent on vascular oxygenation of the tumors. Knowledge of the kinetics of tracer uptake as well as vascular oxygenation is essential to make an informed assessment of glucose demand of a tumor

Modeling the Cellular Response of Lung Cancer to Radiation Therapy for a Broad Range of Fractionation Schedules

Purpose: To demonstrate that a mathematical model can be used to quantitatively understand tumor cellular dynamics during a course of radiotherapy and to predict the likelihood of local control as a function of dose and treatment fractions.Experimental Design: We model outcomes for early-stage, localized non-small cell lung cancer (NSCLC), by fitting a mechanistic, cellular dynamics-based tumor control probability that assumes a constant local supply of oxygen and glucose. In addition to standard radiobiological effects such as repair of sub-lethal damage and the impact of hypoxia, we also accounted for proliferation as well as radiosensitivity variability within the cell cycle. We applied the model to 36 published and two unpublished early-stage patient cohorts, totaling 2,701 patients.Results: Precise likelihood best-fit values were derived for the radiobiological parameters: α [0.305 Gy-1; 95% confidence interval (CI), 0.120-0.365], the α/β ratio (2.80 Gy; 95% CI, 0.40-4.40), and the oxygen enhancement ratio (OER) value for intermediately hypoxic cells receiving glucose but not oxygen (1.70; 95% CI, 1.55-2.25). All fractionation groups are well fitted by a single dose-response curve with a high χ2 P value, indicating consistency with the fitted model. The analysis was further validated with an additional 23 patient cohorts (n = 1,628). The model indicates that hypofractionation regimens overcome hypoxia (and cell-cycle radiosensitivity variations) by the sheer impact of high doses per fraction, whereas lower dose-per-fraction regimens allow for reoxygenation and corresponding sensitization, but lose effectiveness for prolonged treatments due to proliferation.Conclusions: This proposed mechanistic tumor-response model can accurately predict overtreatment or undertreatment for various treatment regimens. Clin Cancer Res; 23(18); 5469-79. ©2017 AACR

Effects of high-dose microbeam irradiation on tumor microvascular function and angiogenesis

Microbeam radiation therapy (MRT) is a form of cancer treatment in which a single large dose of radiation is spatially fractionated in-line or grid-like patterns. Preclinical studies have demonstrated that MRT is capable of eliciting high levels of tumor response while sparing normal tissue that is exposed to the same radiation field. Since a large fraction of the MRT-treated tumor is in the dose valley region that is not directly irradiated, tumor response may be driven by radiation bystander effects, which in turn elicit a microvascular response. Differential alterations in hemodynamics between the tumor and normal tissue may explain the therapeutic advantages of MRT. Direct observation of these dynamic responses presents a challenge for conventional ex vivo analysis. Furthermore, knowledge gleaned from in vitro studies of radiation bystander response has not been widely incorporated into in vivo models of tumor radiotherapy, and the biological contribution of the bystander effect within the tumor microenvironment is unknown. In this study, we employed noninvasive, serial observations of the tumor microenvironment to address the question of how tumor vasculature and HIF-1 expression are affected by microbeam radiotherapy. Tumors (approximately 4 mm in diameter) grown in a dorsal window chamber were irradiated in a single fraction using either a single, microplanar beam (300 micron wide swath) or a wide-field setup (whole-window chamber) to a total dose of 50 Gy. The tumors were optically observed daily for seven days postirradiation. Microvascular changes in the tumor and surrounding normal tissue differed greatly between the wide-field and microbeam treatments. We present evidence that these changes may be due to dissimilar spatial and temporal patterns of HIF-1 expression induced through radiation bystander effects

The ratio 2-NBDG/R_D facilitates assessment of glucose demand in heterogeneous regions of metastatic mammary tumors.

<p>(A) Representative images of vascular oxygenation (SO₂) and delivery-corrected 2-NBDG (2-NBDG₆₀/R_D) for a 4T1 tumor with low mean SO₂, a 4T1 tumor with intermediate mean SO₂, and a 4T07 with high mean SO₂. Adapted from Rajaram, et al. 2013. (B) Survival curves (1-cumulative distributions) show 2-NBDG₆₀, R_D, and 2-NBDG₆₀/R_D for regions of distinct SO₂ (%) in 4T07 and 4T1 tumors. For 4T1, 2-NBDG₆₀ is lower for 02,4T1<10 regions than for any other SO_2,4T1 (p = N.S.). Significantly lower rates of R_D are seen for the 02,4T1<10 group than for well-oxygenated 4T1 regions (p<0.05 or p<0.01 for 02,4T1<10 vs. 202,4T1<40 or 402,4T1<60, respectively). After correction for low R_D, 2-NBDG₆₀/R_D increased slightly but significantly in hypoxic regions (p<0.01 for 02,4T1<10 vs. 402,4T1<60). For 4T07, 2-NBDG uptake for the highest SO_2,4T07 regions decreased compared to the lowest SO_2,4T07 (p<0.01 for all 202,4T07<40 vs. 602,4T1<80). R_D is indistinguishable between SO_2,4T07 levels. After correction by R_D, 2-NBDG₆₀/R_D is lowest for 602,4T07<80 (p<0.01). Comparison between 4T1 and 4T07 shows that 2-NBDG₆₀ is higher for all SO_2,4T1 than all SO_2,4T07 (p<0.01). On the other hand, R_D for the best oxygenated 4T07 groups (402,4T07<60 and 602,4T07<80) is greater than for all 4T1 groups (p<0.01 for all groups except 402,4T1<60 vs. 602,4T07<80 where p<0.06). After correction by R_D, 2-NBDG₆₀/R_D is higher for all SO_2,4T1 than all SO_2,4T07 (p<0.01 for all SO_2,4T1 compared to all SO_2,4T07). Number of mice per group indicated by group name in legend.</p

The rate of 2-NBDG delivery, R_D, is strongly correlated with blood velocity.

<p>(A) Representative images of blood velocity and the rate of 2-NBDG delivery (R_D) in a normal mouse at baseline and during reoxygenation after 1 hour of hypoxia. (B) Paired data for a set of mice at baseline and after 1 hour of hypoxia. After hypoxia, flow velocity and R_D increased significantly (p<0.02 for both). N = 6 mice. (C) The rate of 2-NBDG delivery (R_D) is highly correlated with blood velocity (R = 0.87, p<0.05). The trendline corresponds to the trend for post-hypoxia data only.</p