Q & A with Daniel L. Hartl, Recipient of the 2019 Thomas Hunt Morgan Medal.

The Genetics Society of America's Thomas Hunt Morgan Medal honors researchers for lifetime achievement in genetics. The recipient of the 2019 Morgan Medal is Daniel Hartl of Harvard University, who is recognized for his influential and diverse contributions to genetics research. The unifying theme of Hartl's broad impacts on transmission, population, evolutionary, and medical genetics has been the combination of theoretical insights with cutting-edge experimental techniques. Some of his contributions include revealing the genetics of segregation distortion, developing statistical frameworks for estimating the effects of selection, application of these frameworks to natural and experimental populations, discovery of the mariner transposon and its influence on genome evolution, insights into the evolution of gene expression differences, and modeling the evolution of malaria parasite populations. Hartl is also known as a supportive mentor who has trained many prominent geneticists that continue to shape the field.

Ion Channels: History, Diversity, and Impact.

From patch-clamp techniques to recombinant DNA technologies, three-dimensional protein modeling, and optogenetics, diverse and sophisticated methods have been used to study ion channels and how they determine the electrical properties of cells.

Organoids: A historical perspective of thinking in three dimensions.

In the last ten years, there has been a dramatic surge in the number of publications where single or groups of cells are grown in substrata that have elements of basement membrane leading to the formation of tissue-like structures referred to as organoids. However, this field of research began many decades ago, when the pioneers of cell culture began to ask questions we still ask today: How does organogenesis occur? How do signals integrate to make such vastly different tissues and organs given that the sequence of the genome in our trillions of cells is identical? Here, we summarize how work over the past century generated the conceptual framework that has allowed us to make progress in the understanding of tissue-specific morphogenetic programs. The development of cell culture systems that provide accurate and physiologically relevant models are proving to be key in establishing appropriate platforms for the development of new therapeutic strategies.

Citología Papanicolaou 100 años. Un éxito compartido / A hundred years of Papanicolaou cytology: a success shared

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Implementation and Challenges of Direct Acoustic Dosing into Cell-Based Assays.

Since the adoption of Labcyte Echo Acoustic Droplet Ejection (ADE) technology by AstraZeneca in 2005, ADE has become the preferred method for compound dosing into both biochemical and cell-based assays across AstraZeneca research and development globally. The initial implementation of Echos and the direct dosing workflow provided AstraZeneca with a unique set of challenges. In this article, we outline how direct Echo dosing has evolved over the past decade in AstraZeneca. We describe the practical challenges of applying ADE technology to 96-well, 384-well, and 1536-well assays and how AstraZeneca developed and applied software and robotic solutions to generate fully automated and effective cell-based assay workflows.

Tecnologia e campos disciplinares: os citotécnicos e a implementação do teste de Papanicolaou no Brasil / Technology and disciplinary fields: cytotechnicians and implementation of the Pap test in Brazil

A apropriação e utilização do teste de Papanicolaou como tecnologia fundamental para o controle do câncer de colo do útero no Brasil foi fruto de escolhas, acordos e embates entre determinados grupos profissionais (médicos de diferentes especialidades, farmacêuticos, biólogos, biomédicos e citotécnicos). Na primeira parte do trabalho apresentamos o processo de formulação das primeiras campanhas de rastreamento populacional com uso do teste Papanicolaou no país e, consequentemente, o surgimento da profissão de citotécnicos (profissionais dedicados a leitura das lâminas de Papanicolaou). Num segundo momento, partimos de algumas questões levantadas pela historiografia internacional no campo da história das ciências e das técnicas para discutimos as peculiaridades do processo de apropriação do teste Papanicolaou no contexto brasileiro. Priorizamos as questões relativas aos debates entre diferentes grupos profissionais envolvidos com a lógica desse exame e às relações entre os setores públicos e privados de saúde. Demonstramos que as visões distintas sobre essa tecnologia no campo de diferentes disciplinas e a relação destas com a dinâmica do mercado de trabalho moldam a trajetória da profissão de citotécnico e a forma como o teste de Papanicolaou foi (e está sendo)apropriado como tecnologia central para o rastreio do câncer de colo do útero no Brasil (AU)

The implementation of the Pap test as a primary technology in the control of cervical cancer in Brazil was the result of choices, agreements and disputes among certain professional groups, including physicians from various specialisations, pharmacists, biologists, biomedical scientists and cytotechnologists. The first part of the paper describes the process of formulating Brazil’s first screening campaigns using the Pap smear, and the subsequent emergence of the profession of cytotechnology, whose practitioners interpret this test. Second, based on questions raised by international historiography in the field of science and technology, we explore in detail how the adoption of the Pap smear transpired within the Brazilian context, focussing on the debates among the various professional groups with an interest in the suitability of the test and on the relationships between the public and private healthcare sectors. We show that the professional career of cytotechnologists and the way in which the Pap smear has been implemented as a central technology for cervical cancer screening in Brazil have been shaped by the conflicting views of this technology held by different disciplines as well as by the relationship between these disciplines and labour market dynamics

Controlling female cancer in Argentina. Divergent initiatives and the road to fragmentation

This article analyses the organisation of cancer control in Argentina, with a special focus on the initiatives, institutions, and models that targeted female or gynaecological cancers. It identifies and examines the main factors in the process of elaborating a national policy to control the disease drawing on a series of actors and instruments such as the state, medical professionals, institutions and services, and the use of technology (notably diagnostic tools) for the detection of the disease. It traces the developments in the organisation highlighting its transformations from a centralising to a decentralised model of service provision. Using the concept of «path-dependence» the article examines the continuities and changes observed in the organisation of female cancer critically signalling the particular time at which a path was taken where «fragmentation» became consolidated within the health system. It also argues that it was within the field of cancer diagnosis that Argentinian doctors first sought to create the foundational structures of cancer organisation. The article contends that the path-dependence analytical approach helps us acknowledge the importance of historical analysis in the identification of factors that led to the lack of service coordination, including the persistent strain between national/provincial states that hampered the development of comprehensive programmes, aspects that have continued to mark efforts in the elaboration of cancer policies to the present day (AU)

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La citopatología. Su universalización como método diagnóstico y retos para el patólogo joven / No disponible

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Discovery and rediscoveries of Golgi cells.

When Camillo Golgi invented the black reaction in 1873 and first described the fine anatomical structure of the nervous system, he described a 'big nerve cell' that later took his name, the Golgi cell of cerebellum ('Golgi'schen Zellen', Gustaf Retzius, 1892). The Golgi cell was then proposed as the prototype of type-II interneurons, which form complex connections and exert their actions exclusively within the local network. Santiago Ramón y Cajal (who received the Nobel Prize with Golgi in 1906) proceeded to a detailed description of Golgi cell morphological characteristics, but functional insight remained very limited for many years. The first rediscovery happened in the 1960s, when neurophysiological analysis in vivo revealed that Golgi cells are inhibitory interneurons. This finding promoted the development of two major cerebellar theories, the 'beam theory' of John Eccles and the 'motor learning theory' of David Marr, in which the Golgi cells regulate the spatial organisation and the gain of input signals to be processed and learned by the cerebellar circuit. However, the matter was not set and a series of pioneering observations using single unit recordings and electronmicroscopy raised new issues that could not be fully explored until the 1990s. Then, the advent of new electrophysiological and imaging techniques in vitro and in vivo demonstrated the cellular and network activities of these neurons. Now we know that Golgi cells, through complex systems of chemical and electrical synapses, effectively control the spatio-temporal organisation of cerebellar responses. The Golgi cells regulate the timing and number of spikes emitted by granule cells and coordinate their coherent activity. Moreover, the Golgi cells regulate the induction of long-term synaptic plasticity along the mossy fibre pathway. Eventually, the Golgi cells transform the granular layer of cerebellum into an adaptable spatio-temporal filter capable of performing several kinds of logical operation. After more than a century, Golgi's intuition that the Golgi cell had to generate under a new perspective complex ensemble effects at the network level has finally been demonstrated.