Adaptable P body physical states differentially regulate bicoid mRNA storage during early Drosophila development.

Ribonucleoprotein condensates can exhibit diverse physical states in vitro and in vivo. Despite considerable progress, the relevance of condensate physical states for in vivo biological function remains limited. Here, we investigated the physical properties of processing bodies (P bodies) and their impact on mRNA storage in mature Drosophila oocytes. We show that the conserved DEAD-box RNA helicase Me31B forms viscous P body condensates, which adopt an arrested physical state. We demonstrate that structurally distinct proteins and protein-protein interactions, together with RNA, regulate the physical properties of P bodies. Using live imaging and in situ hybridization, we show that the arrested state and integrity of P bodies support the storage of bicoid (bcd) mRNA and that egg activation modulates P body properties, leading to the release of bcd for translation in the early embryo. Together, this work provides an example of how physical states of condensates regulate cellular function in development.

Granule regulation by phase separation during Drosophila oogenesis.

Drosophila eggs are highly polarised cells that use RNA-protein complexes to regulate storage and translational control of maternal RNAs. Ribonucleoprotein granules are a class of biological condensates that form predominantly by intracellular phase separation. Despite extensive in vitro studies testing the physical principles regulating condensates, how phase separation translates to biological function remains largely unanswered. In this perspective, we discuss granules in Drosophila oogenesis as a model system for investigating the physiological role of phase separation. We review key maternal granules and their properties while highlighting ribonucleoprotein phase separation behaviours observed during development. Finally, we discuss how concepts and models from liquid-liquid phase separation could be used to test mechanisms underlying granule assembly, regulation and function in Drosophila oogenesis.

RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration.

Human Ataxin-2 is implicated in the cause and progression of amyotrophic lateral sclerosis (ALS) and type 2 spinocerebellar ataxia (SCA-2). In Drosophila, a conserved atx2 gene is essential for animal survival as well as for normal RNP-granule assembly, translational control, and long-term habituation. Like its human homolog, Drosophila Ataxin-2 (Atx2) contains polyQ repeats and additional intrinsically disordered regions (IDRs). We demonstrate that Atx2 IDRs, which are capable of mediating liquid-liquid phase transitions in vitro, are essential for efficient formation of neuronal mRNP assemblies in vivo. Remarkably, ΔIDR mutants that lack neuronal RNP granules show normal animal development, survival, and fertility. However, they show defects in long-term memory formation/consolidation as well as in C9ORF72 dipeptide repeat or FUS-induced neurodegeneration. Together, our findings demonstrate (1) that higher-order mRNP assemblies contribute to long-term neuronal plasticity and memory, and (2) that a targeted reduction in RNP-granule formation efficiency can alleviate specific forms of neurodegeneration.

Flow studies in three-dimensional aorto-right coronary bypass graft system.

This paper presents the fluid dynamics of blood flow in a coronary bypass model of the aorto-right coronary bypass system. Three-dimensional computational fluid dynamic simulations are developed of the blood flow in coronary artery-bypass systems, using the computational fluid dynamics software (FLUENT 6.0.1). These blood flow simulations are performed within small intervals of the cardiac cycle, using input data consisting of physiological measurements of flow rates in the aorta, obtained from earlier studies. We have calculated the flow-field distributions of the velocity and the wall shear stress at four typical instants of the cardiac cycle, two during systole and two during the diastole phase. Plots of velocity vector and the wall shear stress are displayed in the aorto-graft-coronary arterial flow-field domain, providing an insight into the link between fluid dynamics and arterial diseases. The prime regions of disturbed flow patterns are at the entrance into the graft from the aorta and at the exit from the graft into the right coronary artery. Our objective is to obtain an understanding of how the coronary artery is perfused by the graft, and thereby into the factors affecting graft patency.

Comparison of oral squamous cell carcinoma in younger and older patients in India.

This study examines the demographic, aetiological and clinico-pathological features of 37 patients with oral squamous cell carcinoma (SCC) who were less than 35 years old and a comparable number of patients who were greater than 60 years old. The study was undertaken at the Regional Cancer Centre, Trivandrum, India, between 1988 and 1990. In patients younger than 35 years old, oral SCC occurred more commonly in females, was apparent in all social classes and was associated with fewer aetiological factors. The tumours manifested predominantly as invasive lesions affecting the tongue and there was early spread to lymph nodes. By contrast, in patients older than 60 years of age, oral SCC was more common in males, occurred more frequently in social classes III and IV and was always seen in association with smoking, alcohol or pan chewing. These latter tumours presented as exophytic lesions of the buccal mucosa or gingivae and spread late to lymph nodes. The results indicate that the biological behaviour of oral SCC in young patients may be distinct from that occurring in older patients.