Data Science in Undergraduate Life Science Education: A Need for Instructor Skills Training.

There is a clear demand for quantitative literacy in the life sciences, necessitating competent instructors in higher education. However, not all instructors are versed in data science skills or research-based teaching practices. We surveyed biological and environmental science instructors (n = 106) about the teaching of data science in higher education, identifying instructor needs and illuminating barriers to instruction. Our results indicate that instructors use, teach, and view data management, analysis, and visualization as important data science skills. Coding, modeling, and reproducibility were less valued by the instructors, although this differed according to institution type and career stage. The greatest barriers were instructor and student background and space in the curriculum. The instructors were most interested in training on how to teach coding and data analysis. Our study provides an important window into how data science is taught in higher education biology programs and how we can best move forward to empower instructors across disciplines.

Salting our freshwater lakes.

The highest densities of lakes on Earth are in north temperate ecosystems, where increasing urbanization and associated chloride runoff can salinize freshwaters and threaten lake water quality and the many ecosystem services lakes provide. However, the extent to which lake salinity may be changing at broad spatial scales remains unknown, leading us to first identify spatial patterns and then investigate the drivers of these patterns. Significant decadal trends in lake salinization were identified using a dataset of long-term chloride concentrations from 371 North American lakes. Landscape and climate metrics calculated for each site demonstrated that impervious land cover was a strong predictor of chloride trends in Northeast and Midwest North American lakes. As little as 1% impervious land cover surrounding a lake increased the likelihood of long-term salinization. Considering that 27% of large lakes in the United States have >1% impervious land cover around their perimeters, the potential for steady and long-term salinization of these aquatic systems is high. This study predicts that many lakes will exceed the aquatic life threshold criterion for chronic chloride exposure (230 mg L-1), stipulated by the US Environmental Protection Agency (EPA), in the next 50 y if current trends continue.

Screening for Breast Cancer: What You Need to Know.

Significant controversy surrounds current recommendations for breast cancer screening. This has resulted in wide variation among national organizations in breast cancer screening guidelines. With the expanding field of breast imaging techniques, risk assessment and genetic testing, it has become clear that the recommendations for breast cancer screening need to be individualized in order to maximize the benefit and minimize harms of screening.

A lake classification concept for a more accurate global estimate of the dissolved inorganic carbon export from terrestrial ecosystems to inland waters.

The magnitude of lateral dissolved inorganic carbon (DIC) export from terrestrial ecosystems to inland waters strongly influences the estimate of the global terrestrial carbon dioxide (CO2) sink. At present, no reliable number of this export is available, and the few studies estimating the lateral DIC export assume that all lakes on Earth function similarly. However, lakes can function along a continuum from passive carbon transporters (passive open channels) to highly active carbon transformers with efficient in-lake CO2 production and loss. We developed and applied a conceptual model to demonstrate how the assumed function of lakes in carbon cycling can affect calculations of the global lateral DIC export from terrestrial ecosystems to inland waters. Using global data on in-lake CO2 production by mineralization as well as CO2 loss by emission, primary production, and carbonate precipitation in lakes, we estimated that the global lateral DIC export can lie within the range of [Formula: see text] to [Formula: see text] Pg C yr-1 depending on the assumed function of lakes. Thus, the considered lake function has a large effect on the calculated lateral DIC export from terrestrial ecosystems to inland waters. We conclude that more robust estimates of CO2 sinks and sources will require the classification of lakes into their predominant function. This functional lake classification concept becomes particularly important for the estimation of future CO2 sinks and sources, since in-lake carbon transformation is predicted to be altered with climate change.

Dynamic Changes in Local Protein Synthetic Machinery in Regenerating Central Nervous System Axons after Spinal Cord Injury.

Intra-axonal localization of mRNAs and protein synthesis machinery (PSM) endows neurons with the capacity to generate proteins locally, allowing precise spatiotemporal regulation of the axonal response to extracellular stimuli. A number of studies suggest that this local translation is a promising target to enhance the regenerative capacity of damaged axons. Using a model of central nervous system (CNS) axons regenerating into intraspinal peripheral nerve grafts (PNGs) we established that adult regenerating CNS axons contain several different mRNAs and protein synthetic machinery (PSM) components in vivo. After lower thoracic level spinal cord transection, ascending sensory axons regenerate into intraspinal PNGs but axon growth is stalled when they reach the distal end of the PNG (3 versus 7 weeks after grafting, resp.). By immunofluorescence with optical sectioning of axons by confocal microscopy, the total and phosphorylated forms of PSMs are significantly lower in stalled compared with actively regenerating axons. Reinjury of these stalled axons increased axonal localization of the PSM proteins, indicative of possible priming for a subcellular response to axotomy. These results suggest that axons downregulate protein synthetic capacity as they cease growing, yet they retain the ability to upregulate PSM after a second injury.

Non-motor parkinsonian pathology in aging A53T α-synuclein mice is associated with progressive synucleinopathy and altered enzymatic function.

Aging, the main risk factor for Parkinson's disease (PD), is associated with increased α-synuclein levels in substantia nigra pars compacta (SNc). Excess α-synuclein spurs Lewy-like pathology and dysregulates the activity of protein phosphatase 2A (PP2A). PP2A dephosphorylates many neuroproteins, including the catecholamine rate-limiting enzyme, tyrosine hydroxylase (TH). A loss of nigral dopaminergic neurons induces PD movement problems, but before those abnormalities occur, behaviors such as olfactory loss, anxiety, and constipation often manifest. Identifying mouse models with early PD behavioral changes could provide a model in which to test emerging therapeutic compounds. To this end, we evaluated mice expressing A53T mutant human (A53T) α-synuclein for behavior and α-synuclein pathology in olfactory bulb, adrenal gland, and gut. Aging A53T mice exhibited olfactory loss and anxiety that paralleled olfactory and adrenal α-synuclein aggregation. PP2A activity was also diminished in olfactory and adrenal tissues harboring insoluble α-synuclein. Low adrenal PP2A activity co-occurred with TH hyperactivity, making this the first study to link adrenal synucleinopathy to anxiety and catecholamine dysregulation. Aggregated A53T α-synuclein recombinant protein also had impaired stimulatory effects on soluble recombinant PP2A. Collectively, the data identify an excellent model in which to screen compounds for their ability to block the spread of α-synuclein pathology associated with pre-motor stages of PD.

Preventing overexploitation in a mutualism: partner regulation in the crayfish-branchiobdellid symbiosis.

For a symbiosis to be a mutualism, benefits received must exceed costs incurred for both partners. Partners can prevent costly overexploitation through behaviors that moderate interactions with the other symbiont. In a symbiosis between crayfish and branchiobdellidan annelids, the worms can increase crayfish survival and growth by removing fouling material from the gills. However, overexploitation by the worms is possible and results in damage to host gills. We used behavioral observations to assess the degree to which two species of crayfish (Cambarus chasmodactylus and Orconectes cristavarius) use grooming to moderate their interaction with branchiobdellids. We found that grooming could effectively reduce worm numbers, and the proportion of total grooming directed at worms differed between crayfish species and as a function of worm number. O. cristavarius increased grooming in response to the addition of a single worm, while C. chasmodactylus only increased grooming in response to ten worms. These differences in the number of worms that trigger grooming behavior reflect differences between crayfish species in field settings. We also assessed whether antibacterial compounds in circulating crayfish hemolymph could limit bacterial gill fouling. O. cristavarius hemolymph inhibited some test bacteria more effectively than C. chasmodactylus did. Differences in the antibacterial properties of crayfish hemolymph may therefore help explain differences in both worm-directed grooming and worm loads in the field. We conclude that crayfish can use grooming to reduce worm numbers, which could lower the potential for gill damage, and that the level of grooming varies between crayfish species.

The fine line between mutualism and parasitism: complex effects in a cleaning symbiosis demonstrated by multiple field experiments.

Ecological theory and observational evidence suggest that symbiotic interactions such as cleaning symbioses can shift from mutualism to parasitism. However, field experimental evidence documenting these shifts has never been reported for a cleaning symbiosis. Here, we demonstrate shifts in a freshwater cleaning symbiosis in a system involving crayfish and branchiobdellid annelids. Branchiobdellids have been shown to benefit their hosts under some conditions by cleaning material from host crayfish's gill filaments. The system is uniquely suited as an experimental model for symbiosis due to ease of manipulation and ubiquity of the organisms. In three field experiments, we manipulated densities of worms on host crayfish and measured host growth in field enclosures. In all cases, the experiments revealed shifts from mutualism to parasitism: host crayfish growth was highest at intermediate densities of branchiobdellid symbionts, while high symbiont densities led to growth that was lower or not significantly different from 0-worm controls. Growth responses were consistent even though the three experiments involved different crayfish and worm species and were performed at different locations. Results also closely conformed to a previous laboratory experiment using the same system. The mechanism for these shifts appears to be that branchiobdellids switched from cleaning host gills at intermediate densities of worms to consuming host gill tissue at high densities. These outcomes clearly demonstrate shifts along a symbiosis continuum with the maximum benefits to the host at intermediate symbiont densities. At high symbiont densities, benefits to the host disappear, and there is some evidence for a weak parasitism. These are the first field experimental results to demonstrate such shifts in a cleaning symbiosis.

Strong effects of a mutualism on freshwater community structure.

Numerous mutualisms have been described from terrestrial and marine communities and many of these mutualisms have significant effects on community structure and function. In contrast, there are far fewer examples of mutualisms from freshwater habitats and there is no evidence that any mutualism has community-wide or ecosystem-level consequences. Northern hemisphere crayfish are host to a variety of ectosymbiotic worms called branchiobdellidans. The association between some of these "crayfish worms" and their hosts is a mutualism. The outcome of the association is context dependent and can be influenced by host size, symbiont number, and the environment. Here we document in two experiments that the mutualism between crayfish and these worms alters the effect of crayfish on stream community structure and sediment deposition, an important ecosystem variable. We enclosed crayfish stocked with 0 worms and intermediate (3-6) and high worm densities (12) in cages in streams in Boone, North Carolina and Clemson, South Carolina, United States. At both locations, there was a negative relationship between initial worm density and final macroinvertebrate abundance. There was a significant effect of worm treatment on macroinvertebrate community structure in both the Boone and Clemson experiments. In Boone, there were effects on both overall macroinvertebrate abundance and community composition, whereas in Clemson, changes to community structure were primarily driven by changes in total abundance. There was a negative relationship between benthic sediment volume and initial worm density in both experiments, primarily later in the experiments, though these effects were influenced by sediment deposition rates. Our results are the first to demonstrate strong effects of a mutualism on freshwater communities. Both members of this mutualism are found throughout the northern hemisphere, so similar impacts may occur in many other waterways. Given that various species in addition to crayfish function as keystone species and ecosystem engineers in freshwater systems throughout the world, mutualisms involving these strongly interacting species may be as important to the structure and functioning of freshwater systems as comparable mutualisms in marine and terrestrial systems.

Oxidized Lipoproteins Promote Resistance to Cancer Immunotherapy Independent of Patient Obesity.

Antitumor immunity is impaired in obese mice. Mechanistic insight into this observation remains sparse and whether it is recapitulated in patients with cancer is unclear because clinical studies have produced conflicting and controversial findings. We addressed this by analyzing data from patients with a diverse array of cancer types. We found that survival after immunotherapy was not accurately predicted by body mass index or serum leptin concentrations. However, oxidized low-density lipoprotein (ox-LDL) in serum was identified as a suppressor of T-cell function and a driver of tumor cytoprotection mediated by heme oxygenase-1 (HO-1). Analysis of a human melanoma gene expression database showed a clear association between higher HMOX1 (HO-1) expression and reduced progression-free survival. Our in vivo experiments using mouse models of both melanoma and breast cancer revealed HO-1 as a mechanism of resistance to anti-PD1 immunotherapy but also exposed HO-1 as a vulnerability that could be exploited therapeutically using a small-molecule inhibitor. In conclusion, our clinical data have implicated serum ox-LDL as a mediator of therapeutic resistance in patients with cancer, operating as a double-edged sword that both suppressed T-cell immunity and simultaneously induced HO-1-mediated tumor cell protection. Our studies also highlight the therapeutic potential of targeting HO-1 during immunotherapy, encouraging further translational development of this combination approach.See article by Kuehm et al., p. 227.

Macrosystems EDDIE teaching modules significantly increase ecology students' proficiency and confidence working with ecosystem models and use of systems thinking.

Simulation models are increasingly used by ecologists to study complex, ecosystem-scale phenomena, but integrating ecosystem simulation modeling into ecology undergraduate and graduate curricula remains rare. Engaging ecology students with ecosystem simulation models may enable students to conduct hypothesis-driven scientific inquiry while also promoting their use of systems thinking, but it remains unknown how using hands-on modeling activities in the classroom affects student learning. Here, we developed short (3-hr) teaching modules as part of the Macrosystems EDDIE (Environmental Data-Driven Inquiry & Exploration) program that engage students with hands-on ecosystem modeling in the R statistical environment. We embedded the modules into in-person ecology courses at 17 colleges and universities and assessed student perceptions of their proficiency and confidence before and after working with models. Across all 277 undergraduate and graduate students who participated in our study, completing one Macrosystems EDDIE teaching module significantly increased students' self-reported proficiency, confidence, and likely future use of simulation models, as well as their perceived knowledge of ecosystem simulation models. Further, students were significantly more likely to describe that an important benefit of ecosystem models was their "ease of use" after completing a module. Interestingly, students were significantly more likely to provide evidence of systems thinking in their assessment responses about the benefits of ecosystem models after completing a module, suggesting that these hands-on ecosystem modeling activities may increase students' awareness of how individual components interact to affect system-level dynamics. Overall, Macrosystems EDDIE modules help students gain confidence in their ability to use ecosystem models and provide a useful method for ecology educators to introduce undergraduate and graduate students to ecosystem simulation modeling using in-person, hybrid, or virtual modes of instruction.

Systemic Inhibition of Soluble Tumor Necrosis Factor with XPro1595 Exacerbates a Post-Spinal Cord Injury Depressive Phenotype in Female Rats.

Spinal cord injury (SCI) is associated with a three-fold risk of major depressive disorder compared with the general population. Current antidepressant therapy is often not as effective in this patient population, suggesting the need for a more efficacious therapeutic target. The goal of this study was to elucidate the role of inflammatory cytokine tumor necrosis factor (TNF) in the dorsal raphe nucleus (DRN, the principle source of serotonin to the brain) in the development and possible treatment of depression after SCI. A depressive phenotype following moderate T9 contusion was identified in adult female rats using a battery of behavioral tests (forced swim test, sucrose preference test, novel object recognition test, open field locomotion, and social exploration). Data revealed two clusters of injured rats (58%) that exhibit increased immobility in the forced swim test, indicating depressive phenotype or a melancholic-depressive phenotype with concomitant decrease in sucrose preference. ElevatedTNF levels in the DRN of these two clusters correlated with increased immobility in the forced swim test. We then tested the efficacy of soluble TNF inhibition with XPro1595 treatment to prevent the depressive phenotype after SCI. Subcutaneous (s.c.) delivery of XPro1595 caused an exacerbation of depressive phenotype, with all treated clusters exhibiting increased forced swim immobility compared with saline-treated non-depressed rats. Intracerebroventricular (i.c.v.) administration of the drug did not prevent or enhance the development of depression after injury. These results suggest a complex role for TNF-based neuroinflammation in SCI-induced depression that needs to be further explored, perhaps in conjunction with a broader targeting of additional post-SCI inflammatory cytokines.

Why Has Breast Cancer Screening Failed to Decrease the Incidence of de Novo Stage IV Disease?

: Background: Despite screening mammography, the incidence of Stage IV breast cancer (BC) at diagnosis has not decreased over the past four decades. We previously found that many BCs are small due to favorable biology rather than early detection. This study compared the biology of Stage IV cancers with that of small cancers typically found by screening. Methods: Trends in the incidence of localized, regional, and distant female BC were compared using SEER*Stat. The National Cancer Database (NCDB) was then queried for invasive cancers from 2010 to 2015, and patient/disease variables were compared across stages. Biological variables including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), grade, and lymphovascular invasion were sorted into 48 combinations, from which three biological subtypes emerged: indolent, intermediate, and aggressive. The distributions of the subtypes were compared across disease stages. Multivariable regression assessed the association between Stage IV disease and biology. Results: SEER*Stat confirmed that the incidence of distant BC increased between 1973 and 2015 (annual percent change [APC] = 0.46). NCDB data on roughly 993,000 individuals showed that Stage IV disease at presentation is more common in young, black, uninsured women with low income/education and large, biologically aggressive tumors. The distribution of tumor biology varied by stage, with Stage IV disease including 37.6% aggressive and 6.0% indolent tumors, versus sub-centimeter Stage I disease that included 5.1% aggressive and 40.6% indolent tumors (p < 0.001). The odds of Stage IV disease presentation more than tripled for patients with aggressive tumors (OR3.2, 95% CI 3.0⁻3.5). Conclusions: Stage I and Stage IV breast cancers represent very different populations of biologic tumor types. This may explain why the incidence of Stage IV cancer has not decreased with screening.

Power, pitfalls, and potential for integrating computational literacy into undergraduate ecology courses.

Environmental research requires understanding nonlinear ecological dynamics that interact across multiple spatial and temporal scales. The analysis of long-term and high-frequency sensor data combined with simulation modeling enables interpretation of complex ecological phenomena, and the computational skills needed to conduct these analyses are increasingly being integrated into graduate student training programs in ecology. Despite its importance, however, computational literacy-that is, the ability to harness the power of computer technologies to accomplish tasks-is rarely taught in undergraduate ecology classrooms, representing a major gap in training students to tackle complex environmental challenges. Through our experience developing undergraduate curricula in long-term and high-frequency data analysis and simulation modeling for two environmental science pedagogical initiatives, Project EDDIE (Environmental Data-Driven Inquiry and Exploration) and Macrosystems EDDIE, we have found that students often feel intimidated by computational tasks, which is compounded by the lack of familiarity with software (e.g., R) and the steep learning curves associated with script-based analytical tools. The use of prepackaged, flexible modules that introduce programming as a mechanism to explore environmental datasets and teach inquiry-based ecology, such as those developed for Project EDDIE and Macrosystems EDDIE, can significantly increase students' experience and comfort levels with advanced computational tools. These types of modules in turn provide great potential for empowering students with the computational literacy needed to ask ecological questions and test hypotheses on their own. As continental-scale sensor observatory networks rapidly expand the availability of long-term and high-frequency data, students with the skills to manipulate, visualize, and interpret such data will be well-prepared for diverse careers in data science, and will help advance the future of open, reproducible science in ecology.