Emergent material properties of developing epithelial tissues

Background

Force generation and the material properties of cells and tissues are central to morphogenesis but remain difficult to measure in vivo. Insight is often limited to the ratios of mechanical properties obtained through disruptive manipulation, and the appropriate models relating stress and strain are unknown. The Drosophila amnioserosa epithelium progressively contracts over 3 hours of dorsal closure, during which cell apices exhibit area fluctuations driven by medial myosin pulses with periods of 1.5–6 min. Linking these two timescales and understanding how pulsatile contractions drive morphogenetic movements is an urgent challenge.

Results

We present a novel framework to measure in a continuous manner the mechanical properties of epithelial cells in the natural context of a tissue undergoing morphogenesis. We show that the relationship between apicomedial myosin fluorescence intensity and strain during fluctuations is consistent with a linear behaviour, although with a lag. We thus used myosin fluorescence intensity as a proxy for active force generation and treated cells as natural experiments of mechanical response under cyclic loading, revealing unambiguous mechanical properties from the hysteresis loop relating stress to strain. Amnioserosa cells can be described as a contractile viscoelastic fluid. We show that their emergent mechanical behaviour can be described by a linear viscoelastic rheology at timescales relevant for tissue morphogenesis. For the first time, we establish relative changes in separate effective mechanical properties in vivo. Over the course of dorsal closure, the tissue solidifies and effective stiffness doubles as net contraction of the tissue commences. Combining our findings with those from previous laser ablation experiments, we show that both apicomedial and junctional stress also increase over time, with the relative increase in apicomedial stress approximately twice that of other obtained measures.

Conclusions

Our results show that in an epithelial tissue undergoing net contraction, stiffness and stress are coupled. Dorsal closure cell apical contraction is driven by the medial region where the relative increase in stress is greater than that of stiffness. At junctions, by contrast, the relative increase in the mechanical properties is the same, so the junctional contribution to tissue deformation is constant over time. An increase in myosin activity is likely to underlie, at least in part, the change in medioapical properties and we suggest that its greater effect on stress relative to stiffness is fundamental to actomyosin systems and confers on tissues the ability to regulate contraction rates in response to changes in external mechanics.

     

‘Children are the food sent by God’: culinary imagery and the making of persons in the Cameroon Grassfields

The article explores aspects of personhood as these emerge through rites of passage and culinary imagery in Batié, an eastern Grassfields polity in west Cameroon. Food appears as a gendered medium which, by being exchanged, cooked, and ingested by persons – and by collectives perceived as persons – has the power to transform others (persons and collectives) and make them act. Persons and collectives are revealed, at the different stages of their ceremonial journey, as the outcome of similar processes – exchange, cooking, and ingestion of food – occurring each time on different scales, and thus displaying fractal properties. Introducing a split between agent and (cause of) agency, the article finally suggests that agents’ successive (ritual) transformations are the result of their own actions as well as the actions of (‘individual’ or ‘collective’) others upon them.     

Two New Hydronaphthoquinones from Sinningia aggregata (Gesneriaceae) and Cytotoxic Activity of Aggregatin D

Two new hydronaphthoquinones, aggregatins E and F ( 1 and 2 , resp.) were isolated from the tubers of Sinningia aggregata (Ker‐Gawl .) Wiehler (Gesneriaceae), along with twelve known compounds aggregatin D ( 3 ), tectoquinone ( 4 ), 1‐hydroxy‐2‐methylanthraquinone ( 5 ), icosyl ferulate ( 6 ), pustuline ( 7 ), 1,6‐dihydroxy‐2‐methylanthranquinone ( 8 ), 6‐hydroxy‐2‐methylanthraquinone ( 9 ), 7‐hydroxy‐2‐methylanthraquinone ( 10 ), tyrosol ( 11 ), halleridone ( 12 ), calceolarioside B ( 13 ), and cornoside ( 14 ). All compounds were identified by analysis of spectroscopic and spectrometric data. Compounds 3, 4 , and 10 had already been reported in this species. Compounds 2 and 3 were evaluated against several tumor cell lines, but only 3 exhibited activities against UACC‐62, 786‐0 and OVCAR‐3 cell lines, with IC₅₀ values of 12.3, 12.8 and 0.3 μg/ml, respectively, without toxic effects on non‐cancer cell line HaCat (human keratinocyte).     

Phytochemicals from the genus Lavandula: a review

Phytochemistry Reviews - The genus Lavandula occurs naturally in the Mediterranean basin and its species are a rich source of phytochemicals. Species of this genus have attracted great interest,...     

Rutin improves glutamate uptake and inhibits glutamate excitotoxicity in rat brain slices

Molecular Biology Reports - Rutin is an important flavonoid consumed in the daily diet. It is also known as vitamin P and has been extensively investigated due to its pharmacological properties. On...     

Seasonal Variation in Pollen Catch in a Black Spruce Orchard

Pollen monitoring was conducted over three years (1987–1989) in a 12.4 ha Picea mariana (Mill.) B.S.P. (black spruce) seedling seed orchard established from 1979 to 1984. Pollen traps were installed around and within the orchard and collected daily. Pollen-cone production was highest in 1988 with an average of 0, 11, 20, and 38 cones per tree for 5-, 8-, 9-, and 10-year-old trees. Trees of the oldest section of the orchard bore about 60% of the total number of orchard pollen cones in 1987 and 1988 but only 26% in 1989. Pollen contamination during seed-cone receptivity was important in all three years assessed. The increase in pollen contamination from 1988 to 1989 resulted, in part, from 1) the roguing of 63% of trees in the oldest section of the orchard and 2) a 17-fold decrease in orchard pollen production from 1988 to 1989 compared to a 5-fold decrease from contamination sources.     

Larval retention and dynamics of the prawns Palaemon longirostris H. Milne Edwards and Crangon crangon Linnaeus (Decapoda,Caridea) in the Mira estuary,Portugal

Summary

Palaemon longirostris and Crangon crangon larval and post-larval stages were collected intensively in two 24-h cycles during neap and spring tidal periods in a fixed station located in the mid-Mira estuary (southwest Portugal). In each case, on the previous day, horizontal distribution of larval stages was studied in a series of 20 stations from the mouth of the estuary to near freshwater. Horizontal distribution of the discrete instars of both species were similar, suggesting larval retention. Results from the 24-h cycles indicate a semilunar cycle of larval release activity, and an initial displacement of the larvae from the parental stock, as newly-hatched larvae concentrate in the surface layer of the water column on post-crepuscular ebbing tides. The sequence of larval stages tends to be progressively more dependent of the bottom layers, and the whole larval and post-larval development is accomplished within the estuarine boundaries. Larval release cycles, coupled with duration of development and progressive change in vertical position, induce mutual exclusion of different aged larvae, which may minimise cannibalistic behaviour and competition between larvae with different capabilities.     

Synthesis and Characterization of Novel Quinazoline Type Inhibitors for Mutant and Wild-Type EGFR and RICK Kinases

The development of selective protein kinase inhibitors has become an important area of drug discovery for the treatment of different diseases. We report the synthesis and characterization of a series of novel quinazoline derivatives against three therapeutically important and pharmacologically related kinases: 1) epidermal growth factor receptor (EGFR; wild type and mutant) in the field of cancer, 2) receptor-interacting caspase-like apoptosis-regulatory kinase (RICK) in the field of inflammation, and 3) pUL97 of human cytomegalovirus (HCMV). For reference purpose we have synthesized the four clinically relevant quinazolines, including the lead compounds, which we previously identified for RICK and pUL97. A total of 52 quinazoline derivatives were synthesized and tested on the basis of these leads to specifically target the hydrophobic pocket of the ATP-binding site. Selected compounds were tested on wild-type and mutant forms of EGFR, RICK, and pUL97 kinases; their logP and logS values for assessing suitability as drugs were calculated and hit or lead compounds identified.