Using chemistry and microfluidics to understand the spatial dynamics of complex biological networks

Understanding the spatial dynamics of biochemical networks is both fundamentally important for understanding life at the systems level and also has practical implications for medicine, engineering, biology, and chemistry. Studies at the level of individual reactions provide essential information about the function, interactions, and localization of individual molecular species and reactions in a network. However, analyzing the spatial dynamics of complex biochemical networks at this level is difficult. Biochemical networks are non-equilibrium systems containing dozens to hundreds of reactions with nonlinear and time-dependent interactions, and these interactions are influenced by diffusion, flow, and the relative values of state-dependent kinetic parameters. To achieve an overall understanding of the spatial dynamics of a network and the global mechanisms that drive its function, networks must be analyzed as a whole, where all of the components and influential parameters of a network are simultaneously considered. Here, we describe chemical concepts and microfluidic tools developed for network-level investigations of the spatial dynamics of these networks. Modular approaches can be used to simplify these networks by separating them into modules, and simple experimental or computational models can be created by replacing each module with a single reaction. Microfluidics can be used to implement these models as well as to analyze and perturb the complex network itself with spatial control on the micrometer scale. We also describe the application of these network-level approaches to elucidate the mechanisms governing the spatial dynamics of two networks-hemostasis (blood clotting) and early patterning of the Drosophila embryo. To investigate the dynamics of the complex network of hemostasis, we simplified the network by using a modular mechanism and created a chemical model based on this mechanism by using microfluidics. Then, we used the mechanism and the model to predict the dynamics of initiation and propagation of blood clotting and tested these predictions with human blood plasma by using microfluidics. We discovered that both initiation and propagation of clotting are regulated by a threshold response to the concentration of activators of clotting, and that clotting is sensitive to the spatial localization of stimuli. To understand the dynamics of patterning of the Drosophila embryo, we used microfluidics to perturb the environment around a developing embryo and observe the effects of this perturbation on the expression of Hunchback, a protein whose localization is essential to proper development. We found that the mechanism that is responsible for Hunchback positioning is asymmetric, time-dependent, and more complex than previously proposed by studies of individual reactions. Overall, these approaches provide strategies for simplifying, modeling, and probing complex networks without sacrificing the functionality of the network. Such network-level strategies may be most useful for understanding systems with non-linear interactions where spatial dynamics is essential for function. In addition, microfluidics provides an opportunity to investigate the mechanisms responsible for robust functioning of complex networks. By creating nonideal, stressful, and perturbed environments, microfluidic experiments could reveal the function of pathways thought to be nonessential under ideal conditions

Curie: Constraining Solar System Bombardment Using In Situ Radiometric Dating

The Curie mission would constrain the existence of the putative cataclysm by determining the age of samples directly sourced from the impact melt sheet of a major pre-Imbrium lunar basin. The measurements would also enable further understanding of lunar evolution by characterizing new lunar lithologies far from the Apollo and Luna landing sites, including the very low-Ti basalts in Mare Crisium and potential olivine rich lithologies in the margins of both Mare Nectaris and Mars Crisium. Equipped with a mass spectrometer and a LIBS, Curie would also be well-placed to survey volatile components of the lunar regolith, including surface-bound hydrogen

Desmoplastic small round cell tumour in a 74 year old man: an uncommon cause of ascites (case report)

A rare case is provided of a 74 year old man who presented with ascites of unknown etiology. CT scan of the abdomen revealed extensive omental caking, and omental biopsy cytogenetics showed findings in keeping with a diagnosis of desmoplastic small round cell tumour (DSRCT). This case is unique in that it involves a significantly older patient, negative WT1 immunohistochemical staining, and negative cytology. Despite repeated paracenteses and fluid management, the patient died in hospital secondary to renal complications

Inferring Airflow Across Martian Dunes From Ripple Patterns and Dynamics

Large ripples form striking patterns on the slopes of martian sand dunes which can be mapped and tracked using high-resolution optical images. The ripples vary in orientation, wavelength, plan-view morphology, and rates of migration. The variations in the ripple patterns are recognized to signal the effects of the regional and local winds and feedbacks between winds and dune topography. We examine the ripple patterns and the motion of these ripples to interpret airflow dynamics around dunes in the dune field at Nili Patera. We find that coincident changes in ripple patterns and migration rates in dune wakes indicate reattachment lengths of 4–7 brink heights. This reattachment length is similar to length scales of flow reattachment for airflow over dunes measured on Earth despite the differences in aeolian environment. Furthermore, ripples on dune flanks are shown to behave according to terrestrial models for ripple development on steep slopes. Compensating for these slope effects allows them to act as indicators of dune-modified and regional wind directions. Changes in ripple patterns and migration rates also signal the response of dunes and airflow during dune collisions. Collectively, we find that differences in ripple patterns connected to changes in migration rate provide information on airflow over and around dunes. This detailed assessment of ripple measurement and ripple migration rates advances the use of ripples on martian dunes and sand sheets to infer dune- and field-scale wind dynamics. These measurements also indicate that the low density atmosphere on Mars does not significantly modify the behavior of wind-topography interactions compared to Earth. Such observations provide targets for computational fluid dynamic and large-eddy simulation models seeking to reveal complex airflows across dune fields both on Earth and on Mars

Pluto's Far Side

The New Horizons spacecraft provided near-global observations of Pluto that far exceed the resolution of Earth-based datasets. However, most previous Pluto New Horizons analyses focused on the New Horizons encounter hemisphere (i.e., the anti-Charon hemisphere containing Sputnik Planitia). In this work, we summarize and interpret data on Pluto's “far side” (i.e., its non-encounter or alternatively, its sub-Charon hemisphere), providing the first integrated New Horizons overview of Pluto's far side terrains. We find strong evidence for widespread bladed (i.e., aligned CH₄-mountain) deposits, evidence for an impact crater about as large as any on the “near side” hemisphere, evidence for complex lineations approximately antipodal to Sputnik Planitia that may be causally related, evidence that the far side maculae (i.e., equatorial dark regions) are smaller and more structured than Pluto's encounter hemisphere maculae, and more

Identification of a New Spinel-Rich Lunar Rock Type by the Moon Mineralogy Mapper (M (sup 3))

The canonical characterization of the lunar crust is based principally on available Apollo, Luna, and meteorite samples. The crust is described as an anorthosite-rich cumulate produced by the lunar magma ocean that has been infused with a mix of Mgsuite components. These have been mixed and redistributed during the late heavy bombardment and basin forming events. We report a new rock-type detected on the farside of the Moon by the Moon Mineralogy Mapper (M3) on Chandrayaan-1 that does not easily fit with current crustal evolution models. The rock-type is dominated by Mg-spinel with no detectible pyroxene or olivine present (<5%). It occurs along the western inner ring of Moscoviense Basin as one of several discrete areas that exhibit unusual compositions relative to their surroundings but without morphological evidence for separate processes leading to exposure

Constraining Solar System Bombardment Using In Situ Radiometric Dating

The leading, but contentious, model for lunar impact history includes a pronounced increase in impact events at around 3.9 Ga. This late heavy bombardment would have scarred Mars and the terrestrial planets, influenced the course of biologic evolution on the early Earth, and rearranged the very architecture of our Solar System. But what if it's not true? In the last decade, new observations and sample analyses have reinterpreted basin ages and "pulled the pin" on the cataclysm - we may only have the age of one large basin (Imbrium). The Curie mission would constrain the onset of the cataclysm by determining the age of a major pre-Imbrium lunar basin (Nectaris or Crisium), characterize new lunar lithologies far from the Apollo and Luna landing sites, including the basalts in the basin-filling maria and olivine-rich lithologies in the basin margins, and provide a unique vantage point to assess volatiles in the lunar regolith from dawn to dusk