Knowledge Hidden in Nuances: From Molecules to Society

The Goal: We have discussed the theme of reintegrating biology several times at the national level over several decades (ex. A New Biology for the 21st Century, National Academy of Sciences, 2009). While these discussions are fruitful and certainly the topic may require an adaptive framework, we suggest a fundamental change in how the scientific community approaches this topic. In particular, we propose that biology can only be integrated when the structural, societal and methodological barriers to participation in biology are alleviated. A focus on the average or most prevalent approach or system - whether it is the structure of a protein, a biological process or pathway, or the average scientist - they all end up excluding observations, people, and ideas. In contrast, we propose a focus on and inclusion of nuances will enable us to examine the boundaries and rarer instances whether of topic or of people, enable us to explore, and learn from diversity that is currently unnoticed and may provide new perspectives, insights about the range of possibilities, and solutions to current challenges. By extending this paradigm to our society, including diverse perspectives and experiences may shed light on how we can learn about new ideas, tools, and resources to enhance our collective toolkits and approach solutions for problems we are addressing. The paper will compare the benefits of applying a nuanced approach at a molecular, cellular, organismal, and population levels and then extend this thinking to science and society. We think that including individuals and perspectives that are beyond the current majority/mainstream will enhance our understanding and ability to approach/address problems. Adding nuance to our understanding of science can come from better inclusion and integration. The intended audience for our Vision paper includes the National Science Foundation (NSF), academic and research institutions, and society at large. We hope that NSF has the potential to create and support opportunities for multiscale scientific explorations at the edge of the boundary (outside the averages). Knowledge derived from these observations and analyses can inspire new perspectives and/or solutions that are universally usable. Additionally, other Vision groups in the Reintegrating Biology meetings include topics that could benefit from the vision presented here (space, time, resilience, modelling, communication/signalling, networks, animal learning, biocomplexity). Academic and research institutions may utilize the proposed framework to review their institutional policies that directly or indirectly (via access to resources, opportunities etc.,) restrict collaborations based on interests and expertise. Our hope for society at large is to consider including, sharing, and respecting diverse perspectives and experiences

A study of the norcaradiene-cycloheptatriene equilibrium in a series of azulenones by NMR spectroscopy; the impact of substitution on the position of equilibrium

A systematic investigation of the influence of substitution at positions C-2 and C-3 on the azulenone skeleton, based on NMR characterisation, is discussed with particular focus on the impact of the steric and electronic characteristics of substituents on the position of the norcaradiene-cycloheptatriene (NCD-CHT) equilibrium. Variable temperature (VT) NMR studies, undertaken to enable the resolution of signals for the equilibrating valence tautomers revealed, in addition, interesting shifts in the equilibrium

Modulation of nucleosome dynamics in Huntington's disease

Transcriptional dysregulation and aberrant chromatin remodeling are central features in the pathology of Huntington's disease (HD). In order to more fully characterize these pathogenic events, an assessment of histone profiles and associated gene changes were performed in transgenic N171-82Q (82Q) and R6/2 HD mice. Analyses revealed significant chromatin modification, resulting in reduced histone acetylation with concomitant increased histone methylation, consistent with findings observed in HD patients. While there are no known interventions that ameliorate or arrest HD progression, DNA/RNA-binding anthracyclines may provide significant therapeutic potential by correcting pathological nucleosome changes and realigning transcription. Two such anthracyclines, chromomycin and mithramycin, improved altered nucleosome homeostasis in HD mice, normalizing the chromatin pattern. There was a significant shift in the balance between methylation and acetylation in treated HD mice to that found in wild-type mice, resulting in greater acetylation of histone H3 at lysine 9 and promoting gene transcription. Gene expression profiling in anthracycline-treated HD mice showed molecular changes that correlate with disease correction, such that a subset of downregulated genes were upregulated with anthracycline treatment. Improved nucleosomal dynamics were concurrent with a significant improvement in the behavioral and neuropathological phenotype observed in HD mice. These data show the ability of anthracycline compounds to rebalance epigenetic histone modification and, as such, may provide the rationale for the design of human clinical trials in HD patient

Research productivity and academics’ conceptions of research

This paper asks the question: do people with different levels of research productivity and identification as a researcher think of research differently? It discusses a study that differentiated levels of research productivity among English and Australian academics working in research-intensive environments in three broad discipline areas: science, engineering and technology; social science and humanities; and medicine and health sciences. The paper explores the different conceptions of research held by these academics in terms of their levels of research productivity, their levels of research training, whether they considered themselves an active researcher and a member of a research team, and their disciplinary differences

Adatom Fe(III) on the hematite surface: Observation of a key reactive surface species

The reactivity of a mineral surface is determined by the variety and population of different types of surface sites (e.g., step, kink, adatom, and defect sites). The concept of "adsorbed nutrient" has been built into crystal growth theories, and many other studies of mineral surface reactivity appeal to ill-defined "active sites." Despite their theoretical importance, there has been little direct experimental or analytical investigation of the structure and properties of such species. Here, we use ex-situ and in-situ scanning tunneling microcopy (STM) combined with calculated images based on a resonant tunneling model to show that observed nonperiodic protrusions and depressions on the hematite (001) surface can be explained as Fe in an adsorbed or adatom state occupying sites different from those that result from simple termination of the bulk mineral. The number of such sites varies with sample preparation history, consistent with their removal from the surface in low pH solutions

Suicide tourism in Manhattan, New York City, 1990-2004

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61257/1/gross_suicide_toursism_2007.pd

Does urbanisation lead to parallel demographic shifts across the world in a cosmopolitan plant?

Urbanisation is occurring globally, leading to dramatic environmental changes that are altering the ecology and evolution of species. In particular, the expansion of human infrastructure and the loss and fragmentation of natural habitats in cities is predicted to increase genetic drift and reduce gene flow by reducing the size and connectivity of populations. Alternatively, the ‘urban facilitation model’ suggests that some species will have greater gene flow into and within cities leading to higher diversity and lower differentiation in urban populations. These alternative hypotheses have not been contrasted across multiple cities. Here, we used the genomic data from the GLobal Urban Evolution project (GLUE), to study the effects of urbanisation on non‐adaptive evolutionary processes of white clover (Trifolium repens) at a global scale. We found that white clover populations presented high genetic diversity and no evidence of reduced Ne linked to urbanisation. On the contrary, we found that urban populations were less likely to experience a recent decrease in effective population size than rural ones. In addition, we found little genetic structure among populations both globally and between urban and rural populations, which showed extensive gene flow between habitats. Interestingly, white clover displayed overall higher gene flow within urban areas than within rural habitats. Our study provides the largest comprehensive test of the demographic effects of urbanisation. Our results contrast with the common perception that heavily altered and fragmented urban environments will reduce the effective population size and genetic diversity of populations and contribute to their isolation

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI −16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI −29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View