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The amphibian skin microbiome is an important component of anti-pathogen defense, but the impact of environmental change on the link between microbiome composition and host stress remains unclear. In this study, we used radiotelemetry and host translocation to track microbiome composition and function, pathogen infection, and host stress over time across natural movement paths for the forest-associated treefrog, Boana faber. We found a negative correlation between cortisol levels and putative microbiome function for frogs translocated to forest fragments, indicating strong integration of host stress response and anti-pathogen potential of the microbiome. Additionally, we observed a capacity for resilience (resistance to structural change and functional loss) in the amphibian skin microbiome, with maintenance of putative pathogen-inhibitory function despite major temporal shifts in microbiome composition. Although microbiome community composition did not return to baseline during the study period, the rate of microbiome change indicated that forest fragmentation had more pronounced effects on microbiome composition than translocation alone. Our findings reveal associations between stress hormones and host microbiome defenses, with implications for resilience of amphibians and their associated microbes facing accelerated tropical deforestation. 

Abstract Batrachochytrium salamandrivorans ( Bsal ) is a fungal pathogen of amphibians that is emerging in Europe and could be introduced to North America through international trade or other pathways. To evaluate the risk of Bsal invasion to amphibian biodiversity, we performed dose-response experiments on 35 North American species from 10 families, including larvae from five species. We discovered that Bsal caused infection in 74% and mortality in 35% of species tested. Both salamanders and frogs became infected and developed Bsal chytridiomycosis. Based on our host susceptibility results, environmental suitability conditions for Bsal , and geographic ranges of salamanders in the United States, predicted biodiversity loss is expected to be greatest in the Appalachian Region and along the West Coast. Indices of infection and disease susceptibility suggest that North American amphibian species span a spectrum of vulnerability to Bsal chytridiomycosis and most amphibian communities will include an assemblage of resistant, carrier, and amplification species. Predicted salamander losses could exceed 80 species in the United States and 140 species in North America. 

Teachers grow from sharing their practice and receiving feedback, yet it can be difficult for teachers to welcome others into their classrooms without feeling judged. Observers need to enter teachers’ classrooms projecting respect and value for the challenging work of teaching. In this article, we share an approach to visiting classrooms, called Affirming Learning Walks, that differs in comparison to more typical learning walks, instructional rounds, or classroom observations. Affirming learning walks are hosted by teachers or administrators, conducted with other teachers, designed around eight practices known to support student achievement, and focused only on those productive practices that are present rather than on the absence of practices or areas for improvement. This approach provides an opportunity to value many of a teacher’s practices that are productive and encourages teachers to engage in more of the productive practices because they are highlighted and celebrated. 

National rates of gun violence have risen during the COVID-19 pandemic. There are many contributing factors to this increase, including the compounding consequences of social isolation, unstable housing, decreased economic stability, and ineffective and violent policing of communities of color. The effects of these factors are exacerbated by the pandemic's impact on the provision and availability of psychosocial services for individuals in marginalized communities, particularly those who have been violently injured. Hospital-based violence intervention programs (HVIPs) have been identified as a crucial intervention strategy in reducing repeat violent injury. The ongoing COVID-19 pandemic has engendered, significant barriers in HVIPs' attempts to assist program participants in achieving their health-related and social goals. This research offers insight into the complexities of providing social services during the convergence of two public health crises—COVID-19 and gun violence—at the HVIPs associated with the two busiest trauma centers in the state of Maryland. In considering the effects of inadequate financial support and resources, issues with staffing, and the shift to virtual programming due to restrictions on in-person care, we suggest possible changes to violence prevention programming to increase the quality of care provided to participants in a manner reflective of their unique structural positions. 

Engineered signaling networks can impart cells with new functionalities useful for directing differentiation and actuating cellular therapies. For such applications, the engineered networks must be tunable, precisely regulate target gene expression, and be robust to perturbations within the complex context of mammalian cells. Here, we use bacterial two-component signaling proteins to develop synthetic phosphoregulation devices that exhibit these properties in mammalian cells. First, we engineer a synthetic covalent modification cycle based on kinase and phosphatase proteins derived from the bifunctional histidine kinase EnvZ, enabling analog tuning of gene expression via its response regulator OmpR. By regulating phosphatase expression with endogenous miRNAs, we demonstrate cell-type specific signaling responses and a new strategy for accurate cell type classification. Finally, we implement a tunable negative feedback controller via a small molecule-stabilized phosphatase, reducing output expression variance and mitigating the context-dependent effects of off-target regulation and resource competition. Our work lays the foundation for establishing tunable, precise, and robust control over cell behavior with synthetic signaling networks.

 

Abstract. Knowledge of past ice sheet configurations is useful for informing projections of future ice sheet dynamics and for calibrating ice sheet models. The topology of grounding line retreat in the Ross Sea sector of Antarctica has been much debated, but it has generally been assumed that the modern ice sheet is as small as it has been for more than 100 000 years (Conway et al., 1999; Lee et al., 2017; Lowry et al., 2019; McKay et al., 2016; Scherer et al., 1998). Recent findings suggest that the West Antarctic Ice Sheet (WAIS) grounding line retreated beyond its current location earlier in the Holocene and subsequently readvanced to reach its modern position (Bradley et al., 2015; Kingslake et al., 2018). Here, we further constrain the post-LGM (Last Glacial Maximum) grounding line retreat and readvance in the Ross Sea sector using a two-phase model of radiocarbon input and decay in subglacial sediments from six sub-ice sampling locations. In addition, we reinterpret high basal temperature gradients, measured previously at three sites in this region (Engelhardt, 2004), which we explain as resulting from recent ice shelf re-grounding accompanying grounding line readvance. Atone location – Whillans Subglacial Lake (SLW) – for which a sedimentporewater chemistry profile is known, we estimate the grounding linereadvance by simulating ionic diffusion. Collectively, our analyses indicate that the grounding line retreated over SLW 4300-2500+1500 years ago, and over sites on Whillans Ice Stream (WIS), Kamb Ice Stream (KIS), and Bindschadler Ice Stream (BIS) 4700-2300+1500, 1800-700+2700, and 1700-600+2800 years ago, respectively. The grounding line only recently readvanced back over those sites 1100-100+200, 1500-200+500, 1000-300+200, and 800±100 years ago for SLW, WIS, KIS, and BIS, respectively. The timing of grounding line retreat coincided with a warm period in the mid-Holocene to late Holocene. Conversely, grounding line readvance is coincident with cooling climate in the last 1000–2000 years. Our estimates for the timing of grounding line retreat and readvance are also consistent with relatively low carbon-to-nitrogen ratios measured in our subglacial sediment samples (suggesting a marine source of organic matter) and with the lack of grounding zone wedges in front of modern grounding lines. Based on these results, we propose that the Siple Coast grounding line motions in the mid-Holocene to late Holocene were primarily driven by relatively modest changes in regional climate, rather than by ice sheet dynamics and glacioisostatic rebound, as hypothesized previously (Kingslake et al., 2018). 

Synthetic biology has the potential to bring forth advanced genetic devices for applications in healthcare and biotechnology. However, accurately predicting the behavior of engineered genetic devices remains difficult due to lack of modularity, wherein a device’s output does not depend only on its intended inputs but also on its context. One contributor to lack of modularity is loading of transcriptional and translational resources, which can induce coupling among otherwise independently-regulated genes. Here, we quantify the effects of resource loading in engineered mammalian genetic systems and develop an endoribonuclease-based feedforward controller that can adapt the expression level of a gene of interest to significant resource loading in mammalian cells. Near-perfect adaptation to resource loads is facilitated by high production and catalytic rates of the endoribonuclease. Our design is portable across cell lines and enables predictable tuning of controller function. Ultimately, our controller is a general-purpose device for predictable, robust, and context-independent control of gene expression.