RECENT COST INCREASES: THEIR FUTURE IMPACTS ON AGRICULTURE

Demand and Price Analysis,

Simultaneous randomisation of eight key active site residues in E. coli NfsA to generate superior nitroreductases for prodrug activation

There is a substantial gap between the levels of enzyme activity Nature can evolve and those that scientists can engineer in the lab. This suggests that conventional directed evolution techniques involving incremental improvements in enzyme activity may frequently fail to ascend even local fitness maxima. This is most likely due to an inability of step-wise evolutionary approaches to effectively retain mutations that are beneficial in combination with one another, but on an individual basis are neutral or even slightly deleterious (i.e., exhibit positive epistasis). To overcome this limitation, we are seeking to “jump” straight to an enzyme with peak activity by conducting simultaneous mass randomisation of eight key active site residues in Escherichia coli NfsA, a nitroreductase enzyme that has several diverse applications in biotechnology. Using degenerate codons, we generated a diverse library containing 425 million unique variants. We then applied a powerful selection system using either or both of two recently identified positive selection compounds, which has enabled us to recover a diverse range of highly active nitroreductase variants. These have been screened against a panel of prodrug substrates to identify variants that are improved with specific prodrug substrates of interest. A primary focus has been developing nitroreductases as tools for targeted cell ablation in zebrafish. The basic system involves co-expression of a nitroreductase and fluorescent reporter under the control of a cell type specific promoter in a transgenic fish. Expression of the nitroreductase selectively sensitises target cells to a prodrug which, following nitroreduction, yields a cytotoxic compound that causes precise targeted cell ablation. We have identified several nil-bystander prodrugs that are able to selectively ablate nitroreductase expressing cells with no harm to nearby cells, and have paired these with highly specialised NfsA variants to improve the efficacy and accuracy of cell ablation. We have also screened our mass-randomisation libraries to recover nitroreductases that have non-overlapping prodrug specificities, to be used in a multiplex cell ablation system. This expands upon the previous system, by using pairs of selective nitroreductases and two different prodrugs to facilitate independent ablation of multiple cell types. For example, we have identified a specialist NfsA variant that has activity for tinidazole and not for metronidazole, achieved by including metronidazole as a simultaneous counter-selection during the initial positive selection process. This elegant positive/negative selection eliminated activity with metronidazole, while still ensuring that some level of nitroreductase activity was retained overall

Best Practices in Honors Pedagogy: Teaching Innovation and Community Engagement through Design Thinking

Honors colleges aim to provide unique first-year experiences that promote life skills and emphasize process over product in an interdisciplinary setting that builds community. A two-semester, five-semester-hour course sequence with colloquia tackles these challenges by introducing an entrepreneurial mindset that pushes students toward innovative understanding and building of community. The first iteration includes an introduction to design thinking; identification of wicked problems; collection of data using immersion experiences, interviews, and literature review; and experiments (n = 35) in project-based entrepreneurial methodologies using Lean LaunchPad. The second iteration involves assessment, applied qualitative analysis, out-of-class learning, and peer mentoring. Results provide a framework for developing innovative thinking, an entrepreneurial mindset, and community engagement among first-year students—a design that, the authors conclude, has not only developed in students specific, non-academic skills (such as resiliency and creative self-confidence) but effectively doubled the size (as mandated by the university) of the first-year class. Implications for future iterations are considered, calling for strengthening administrative support, increasing academic/community partnership, and sustaining funding beyond the first year

A review of inclusive business models and their application in aquaculture development

For aquaculture to continue along its current growth trajectory and contribute towards achieving the Sustainable Development Goals, value chains must become more inclusive. Smallholders and other local value chain actors are often constrained by circumstances and market failures in the global aquaculture industry. Integrating these actors into aquaculture value chains through inclusive business models (IBMs) is often touted as a solution to sustainable and ethical trade and business that can generate development outcomes. We reviewed 36 papers under seven business models commonly used in agriculture development to assess their application in aquaculture value chains in lower‐income countries. A global value chain (GVC) analysis is used to unpack the economic and social upgrading objectives of the different IBMs, as well as the types of relational coordination used between actors in the chain to achieve development outcomes. The extent to which these IBMs helped poor actors overcome certain barriers is evaluated with a focus on how they may ensure or be a risk to inclusiveness through the relations and upgrading opportunities evident in their make‐up. The analysis found that the majority of the models focused on economic upgrading over social upgrading. Providing opportunities for the latter is key to achieving the inclusive objectives of IBMs. Greater horizontal coordination between actors can create further opportunities for economic upgrading established under vertical coordination with other nodes upstream and downstream in a value chain. There is a need to further contextualize these models to aquaculture systems and develop clear indicators of inclusiveness

Human Monocytotropic Ehrlichiosis, Missouri

To determine the incidence, clinical and laboratory characteristics, and utility of molecular diagnosis of human monocytotropic ehrlichiosis (HME) in the primary care setting, we conducted a prospective study in an outpatient primary care clinic in Cape Girardeau, Missouri. One hundred and two patients with a history of fever for 3 days (>37.7°C), tick bite or exposure, and no other infectious disease diagnosis were enrolled between March 1997 and December 1999. HME was diagnosed in 29 patients by indirect immunofluorescent antibody assay and polymerase chain reaction (PCR). Clinical and laboratory manifestations included fever (100%), headache (72%), myalgia or arthralgia (69%), chills (45%), weakness (38%), nausea (38%), leukopenia (60%), thrombocytopenia (56%), and elevated aspartate aminotransferase level (52%). Hospitalization occurred in 41% of case-patients. PCR sensitivity was 56%; specificity, 100%. HME is a prevalent, potentially severe disease in southeastern Missouri that often requires hospitalization. Because clinical presentation of HME is nonspecific, PCR is useful in the diagnosis of acute HME

Correction to: Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol

An amendment to this paper has been published and can be accessed via the original articl

National Cancer Institute’s First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Summary and Recommendations from the Organizing Committee

The National Cancer Institute’s First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation was organized and convened to identify, prioritize, and coordinate future research activities related to relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Each of the Workshop’s 6 Working Committees has published individual reports of ongoing basic, translational, and clinical research and recommended areas for future research related to the areas of relapse biology, epidemiology, prevention, and treatment. This document summarizes each committee’s recommendations and suggests 3 major initiatives for a coordinated research effort to address the problem of relapse after allo-HSCT: (1) to establish multicenter correlative and clinical trial networks for basic/translational, epidemiologic, and clinical research; (2) to establish a network of biorepositories for the collection of samples before and after allo-HSCT to aid in laboratory and clinical studies; and (3) to further refine, implement, and study the Workshop-proposed definitions for disease-specific response and relapse and recommendations for monitoring of minimal residual disease. These recommendations, in coordination with ongoing research initiatives and transplantation organizations, provide a research framework to rapidly and efficiently address the significant problem of relapse after allo-HSCT

Best Practices to Diversify Chemistry Faculty

Many academic institutions have looked at various ways to make their faculty a more diverse and inclusive group of people that better reflect the demographic swath of their current and future student bodies. This is even more so important in chemistry departments, where there has long been a discussion on the “leaky pipeline” for women and underrepresented groups. The work presented here examines programs and policies at various departments aimed at increasing the diversity of their faculty applicant pool, and compares them against the reception of the general scientific community by way of applicant demographics and the use of a survey instrument designed to ascertain the advertisement language that lends to a more diverse applicant pool. The combination of these results is then used to generate a list of best practices that administrations and academic search committees can use to improve their ability to attract diverse talent

HIV Drug-resistant Strains as Epidemiologic Sentinels

The decrease in the proportion of drug resistance among newly infected HIV-1 patients may signal a worsening of the epidemic