Virus shapes and buckling transitions in spherical shells

We show that the icosahedral packings of protein capsomeres proposed by Caspar and Klug for spherical viruses become unstable to faceting for sufficiently large virus size, in analogy with the buckling instability of disclinations in two-dimensional crystals. Our model, based on the nonlinear physics of thin elastic shells, produces excellent one parameter fits in real space to the full three-dimensional shape of large spherical viruses. The faceted shape depends only on the dimensionless Foppl-von Karman number \gamma=YR^2/\kappa, where Y is the two-dimensional Young's modulus of the protein shell, \kappa is its bending rigidity and R is the mean virus radius. The shape can be parameterized more quantitatively in terms of a spherical harmonic expansion. We also investigate elastic shell theory for extremely large \gamma, 10^3 < \gamma < 10^8, and find results applicable to icosahedral shapes of large vesicles studied with freeze fracture and electron microscopy.Comment: 11 pages, 12 figure

The role of citizen science in addressing grand challenges in food and agriculture research

The power of citizen science to contribute to both science and society is gaining increased recognition, particularly in physics and biology. Although there is a long history of public engagement in agriculture and food science, the term ‘citizen science’ has rarely been applied to these efforts. Similarly, in the emerging field of citizen science, most new citizen science projects do not focus on food or agriculture. Here, we convened thought leaders from a broad range of fields related to citizen science, agriculture, and food science to highlight key opportunities for bridging these overlapping yet disconnected communities/fields and identify ways to leverage their respective strengths. Specifically, we show that (i) citizen science projects are addressing many grand challenges facing our food systems, as outlined by the United States National Institute of Food and Agriculture, as well as broader Sustainable Development Goals set by the United Nations Development Programme, (ii) there exist emerging opportunities and unique challenges for citizen science in agriculture/food research, and (iii) the greatest opportunities for the development of citizen science projects in agriculture and food science will be gained by using the existing infrastructure and tools of Extension programmes and through the engagement of urban communities. Further, we argue there is no better time to foster greater collaboration between these fields given the trend of shrinking Extension programmes, the increasing need to apply innovative solutions to address rising demands on agricultural systems, and the exponential growth of the field of citizen science.This working group was partially funded from the NCSU Plant Sciences Initiative, College of Agriculture and Life Sciences ‘Big Ideas’ grant, National Science Foundation grant to R.R.D. (NSF no. 1319293), and a United States Department of Food and Agriculture-National Institute of Food and Agriculture grant to S.F.R., USDA-NIFA Post Doctoral Fellowships grant no. 2017-67012-26999.http://rspb.royalsocietypublishing.orghj2018Forestry and Agricultural Biotechnology Institute (FABI

Inhibition of Haspin Kinase Promotes Cell-Intrinsic and Extrinsic Antitumor Activity.

Patients with melanoma resistant to RAF/MEK inhibitors (RMi) are frequently resistant to other therapies, such as immune checkpoint inhibitors (ICI), and individuals succumb to their disease. New drugs that control tumor growth and favorably modulate the immune environment are therefore needed. We report that the small-molecule CX-6258 has potent activity against both RMi-sensitive (RMS) and -resistant (RMR) melanoma cell lines. Haspin kinase (HASPIN) was identified as a target of CX-6258. HASPIN inhibition resulted in reduced proliferation, frequent formation of micronuclei, recruitment of cGAS, and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. In murine models, CX-6258 induced a potent cGAS-dependent type-I IFN response in tumor cells, increased IFNγ-producing CD8 &lt;sup&gt;+&lt;/sup&gt; T cells, and reduced Treg frequency in vivo. HASPIN was more strongly expressed in malignant compared with healthy tissue and its inhibition by CX-6258 had minimal toxicity in ex vivo-expanded human tumor-infiltrating lymphocytes (TIL), proliferating TILs, and in vitro differentiated neurons, suggesting a potential therapeutic index for anticancer therapy. Furthermore, the activity of CX-6258 was validated in several Ewing sarcoma and multiple myeloma cell lines. Thus, HASPIN inhibition may overcome drug resistance in melanoma, modulate the immune environment, and target a vulnerability in different cancer lineages. SIGNIFICANCE: HASPIN inhibition by CX-6258 is a novel and potent strategy for RAF/MEK inhibitor-resistant melanoma and potentially other tumor types. HASPIN inhibition has direct antitumor activity and induces a favorable immune microenvironment