Ribosome Biogenesis Modulates Ty1 Copy Number Control in Saccharomyces cerevisiae.

Transposons can impact the host genome by altering gene expression and participating in chromosome rearrangements. Therefore, organisms evolved different ways to minimize the level of transposition. In Saccharomyces cerevisiae and its close relative S. paradoxus, Ty1 copy number control (CNC) is mediated by the self-encoded restriction factor p22, which is derived from the GAG capsid gene and inhibits virus-like particle (VLP) assembly and function. Based on secondary screens of Ty1 cofactors, we identified LOC1, a RNA localization/ribosome biogenesis gene that affects Ty1 mobility predominantly in strains harboring Ty1 elements. Ribosomal protein mutants rps0bΔ and rpl7aΔ displayed similar CNC-specific phenotypes as loc1Δ, suggesting that ribosome biogenesis is critical for CNC. The level of Ty1 mRNA and Ty1 internal (Ty1i) transcripts encoding p22 was altered in these mutants, and displayed a trend where the level of Ty1i RNA increased relative to full-length Ty1 mRNA. The level of p22 increased in these mutants, and the half-life of p22 also increased in a loc1Δ mutant. Transcriptomic analyses revealed small changes in the level of Ty1 transcripts or efficiency of translation initiation in a loc1Δ mutant. Importantly, a loc1Δ mutant had defects in assembly of Gag complexes and packaging Ty1 RNA. Our results indicate that defective ribosome biogenesis enhances CNC by increasing the level of p22, and raise the possibility for versatile links between VLP assembly, its cytoplasmic environment, and a novel stress response

Patterns of Oral Microbiota Diversity in Adults and Children: A Crowdsourced Population Study.

Oral microbiome dysbiosis has been associated with various local and systemic human diseases such as dental caries, periodontal disease, obesity, and cardiovascular disease. Bacterial composition may be affected by age, oral health, diet, and geography, although information about the natural variation found in the general public is still lacking. In this study, citizen-scientists used a crowdsourcing model to obtain oral bacterial composition data from guests at the Denver Museum of Nature & Science to determine if previously suspected oral microbiome associations with an individual's demographics, lifestyle, and/or genetics are robust and generalizable enough to be detected within a general population. Consistent with past research, we found bacterial composition to be more diverse in youth microbiomes when compared to adults. Adult oral microbiomes were predominantly impacted by oral health habits, while youth microbiomes were impacted by biological sex and weight status. The oral pathogen Treponema was detected more commonly in adults without recent dentist visits and in obese youth. Additionally, oral microbiomes from participants of the same family were more similar to each other than to oral microbiomes from non-related individuals. These results suggest that previously reported oral microbiome associations are observable in a human population containing the natural variation commonly found in the general public. Furthermore, these results support the use of crowdsourced data as a valid methodology to obtain community-based microbiome data

In Pursuit of Good & Gold: Data Observations of Employee Ownership & Impact Investment

A startup\u27s path to self-sustaining profitability is risky and hard, and most do not make it. Venture capital (VC) investors try to improve these odds with contractual terms that focus and sharpen employees\u27 incentives to pursue gold. If the employees and investors expect the startup to balance the goal of profitability with another goal - the goal of good - the risks are likely to both grow and multiply. They grow to the extent that profits are threatened, and they multiply to the extent that balancing competing goals adds a dimension to the incentive problem. In this Article, we explore contracting terms specific to impact investing funds and their portfolio companies. We observe one possible private ordering mechanism to balance and align interests to serve both goals: employee ownership. Traditional VC investments confront contracting challenges as the portfolio companies and investors balance their interests, which may not align. The VC contracting literature identifies several agency costs that contractual terms can address. Contracts can help attract the right employees, then encourage them to work, stay, and share their best ideas. But, the existing literature addresses traditional agency costs with respect to the pursuit of a single monetary goal. Impact investment funds that balance monetary goals, short-term or long, with other goals may strike a different balance in negotiating with companies. We examine how the introduction of new motivations and interests into a precarious negotiation process shapes contracting outcomes. We address this question empirically by analyzing the role of employee stock ownership in impact investment fund contracts when investing in targeted portfolio companies. That a startup\u27s employees might receive shares and options is uncontroversial. Indeed, this appears in many ways to be fundamental to today\u27s startup culture. Might impact investors mandate that employees own shares as a means to balance dual goals? That is the key question for our analysis

A systematic review of participatory scenario planning to envision mountain social-ecological systems futures

Mountain social-ecological systems (MtSES) provide crucial ecosystem services to over half of humanity. However, populations living in these highly varied regions are now confronted by global change. It is critical that they are able to anticipate change to strategically manage resources and avoid potential conflict. Yet, planning for sustainable, equitable transitions for the future is a daunting task, considering the range of uncertainties and the unique character of MtSES. Participatory scenario planning (PSP) can help MtSES communities by critically reflecting on a wider array of innovative pathways for adaptive transformation. Although the design of effective approaches has been widely discussed, how PSP has been employed in MtSES has yet to be examined. Here, we present the first systematic global review of single- and multiscalar, multisectoral PSP undertaken in MtSES, in which we characterize the process, identify strengths and gaps, and suggest effective ways to apply PSP in MtSES. We used a nine-step process to help guide the analysis of 42 studies from 1989 screened articles. Our results indicate a steady increase in relevant studies since 2006, with 43% published between 2015 and 2017. These studies encompass 39 countries, with over 50% in Europe. PSP in MtSES is used predominantly to build cooperation, social learning, collaboration, and decision support, yet meeting these objectives is hindered by insufficient engagement with intended end users. MtSES PSP has focused largely on envisioning themes of governance, economy, land use change, and biodiversity, but has overlooked themes such as gender equality, public health, and sanitation. There are many avenues to expand and improve PSP in MtSES: to other regions, sectors, across a greater diversity of stakeholders, and with a specific focus on MtSES paradoxes. Communicating uncertainty, monitoring and evaluating impacts, and engendering more comparative approaches can further increase the utility of PSP for addressing MtSES challenges, with lessons for other complex social-ecological systems

Perfluorinated alkyl acids and fecundity assessment in striped mullet (\u3ci\u3eMugil cephalus\u3c/i\u3e) at Merritt Island national wildlife refuge

This study investigated wild caught striped mullet (Mugil cephalus) at Merritt Island National Wildlife Refuge (MINWR) for levels of 15 perfluoroalkyl acids (PFAA) in tandem with individual fecundity measurements (Oocyte sub-stage 2 late, n=42) and oocyte reproductive stages (Stages 1–5, n=128). PFAAmeasurementswere quantified in stripedmullet liver (n=128),muscle (n=49), and gonad (n=10). No significant negative impacts of liver PFAA burden on wild-caught,mullet fecundity endpoints were observed in this study; however, changes in PFAAwere observed in the liver asmullet progressed through different sub-stages of oocyte development. Of the PFAA with significant changes by sub-stage of oocyte development, the carboxylic acids (perfluorooctanoic acid, perfluorononanoic acid, and perfluorotridecanoic acid) increased in the liver with increasing sub-stage while the sulfonic acid and its precursor (perfluorooctanesulfonic acid (PFOS) and perfluorooctanesulfonamide, respectively) decreased in the liver with increasing sub-stage of oocyte development. This is a unique find and suggests PFAA change location of compartmentalization as mullet progress towards spawning. Investigations also revealed higher than expected median muscle and gonad levels of PFOS in striped mullet collected at MINWR (9.01 ng/g and 80.2 ng/g, respectively)

Linking model design and application for transdisciplinary approaches in social-ecological systems

This work was supported by the US National Science Foundation through the Mountain Sentinels Research Coordination Network (NSF #1414106), the Swiss National Science Foundation through MtnPaths – Pathways for global change adaptation of mountain socio-ecological systems (#20521L_169916), and the Center for Collaborative Conservation at Colorado State University.As global environmental change continues to accelerate and intensify, science and society are turning to trans- disciplinary approaches to facilitate transitions to sustainability. Modeling is increasingly used as a technological tool to improve our understanding of social-ecological systems (SES), encourage collaboration and learning, and facilitate decision-making. This study improves our understanding of how SES models are designed and applied to address the rising challenges of global environmental change, using mountains as a representative system. We analyzed 74 peer-reviewed papers describing dynamic models of mountain SES, evaluating them according to characteristics such as the model purpose, data and model type, level of stakeholder involvement, and spatial extent/resolution. Slightly more than half the models in our analysis were participatory, yet only 21.6% of papers demonstrated any direct outreach to decision makers. We found that SES models tend to under-represent social datasets, with ethnographic data rarely incorporated. Modeling efforts in conditions of higher stakeholder diversity tend to have higher rates of decision support compared to situations where stakeholder diversity is absent or not addressed. We discuss our results through the lens of appropriate technology, drawing on the concepts of boundary objects and scalar devices from Science and Technology Studies. We propose four guiding principles to facilitate the development of SES models as appropriate technology for transdisciplinary applications: (1) increase diversity of stakeholders in SES model design and application for improved collaboration; (2) balance power dynamics among stakeholders by incorporating diverse knowledge and data types; (3) promote flexibility in model design; and (4) bridge gaps in decision support, learning, and communication. Creating SES models that are appropriate tech- nology for transdisciplinary applications will require advanced planning, increased funding for and attention to the role of diverse data and knowledge, and stronger partnerships across disciplinary divides. Highly contextualized participatory modeling that embraces diversity in both data and actors appears poised to make strong contributions to the world’s most pressing environmental challenges.PostprintPeer reviewe

Tertiary-Treated Municipal Wastewater is a Significant Point Source of Antibiotic Resistance Genes Into Duluth-Superior Harbor

In this study, the impact of tertiary-treated municipal wastewater on the quantity of several antibiotic resistance determinants in Duluth-Superior Harbor was investigated by collecting surface water and sediment samples from 13 locations in Duluth-Superior Harbor, the St. Louis River, and Lake Superior. Quantitative PCR (qPCR) was used to target three different genes encoding resistance to tetracycline (tet(A), tet(X), and tet(W)), the gene encoding the integrase of class 1 integrons (intI1), and total bacterial abundance (16S rRNA genes) as well as total and human fecal contamination levels (16S rRNA genes specific to the genus Bacteroides). The quantities of tet(A), tet(X), tet(W), intI1, total Bacteroides, and human-specific Bacteroides were typically 20-fold higher in the tertiary-treated wastewater than in nearby surface water samples. In contrast, the quantities of these genes in the St. Louis River and Lake Superior were typically below detection. Analysis of sequences of tet(W) gene fragments from four different samples collected throughout the study site supported the conclusion that tertiary-treated municipal wastewater is a point source of resistance genes into Duluth-Superior Harbor. This study demonstrates that the discharge of exceptionally treated municipal wastewater can have a statistically significant effect on the quantities of antibiotic resistance genes in otherwise pristine surface waters

Electrophysiological Properties of Embryonic Stem Cell-Derived Neurons

In vitro generation of functional neurons from embryonic stem (ES) cells and induced pluripotent stem cells offers exciting opportunities for dissecting gene function, disease modelling, and therapeutic drug screening. To realize the potential of stem cells in these biomedical applications, a complete understanding of the cell models of interest is required. While rapid advances have been made in developing the technologies for directed induction of defined neuronal subtypes, most published works focus on the molecular characterization of the derived neural cultures. To characterize the functional properties of these neural cultures, we utilized an ES cell model that gave rise to neurons expressing the green fluorescent protein (GFP) and conducted targeted whole-cell electrophysiological recordings from ES cell-derived neurons. Current-clamp recordings revealed that most neurons could fire single overshooting action potentials; in some cases multiple action potentials could be evoked by depolarization, or occurred spontaneously. Voltage-clamp recordings revealed that neurons exhibited neuronal-like currents, including an outward current typical of a delayed rectifier potassium conductance and a fast-activating, fast-inactivating inward current, typical of a sodium conductance. Taken together, these results indicate that ES cell-derived GFP+ neurons in culture display functional neuronal properties even at early stages of differentiation

Titration of C-5 Sterol Desaturase Activity Reveals Its Relationship to Candida albicans Virulence and Antifungal Susceptibility Is Dependent upon Host Immune Status

Mutations that completely inactivate Erg3p enable the prevalent human pathogen C. albicans to endure the azole antifungals in vitro . However, such null mutants are less frequently identified in azole-resistant clinical isolates than other resistance mechanisms, and previous studies have reported conflicting outcomes regarding antifungal resistance of these mutants in animal models of infection