Photosynthetic regulation in response to strontium stress in moss Racomitrium japonicum L.

Strontium (Sr2+) pollution and its biological effects are of great concern including photosynthetic regulation, which is fundamental to environmental responses, especially for bryophytes during their terrestrial adaptation. Alternative electron flows mediated by flavodiiron proteins (FLVs) and cyclic electron flow (CEF) in photosystem I (PSI) are crucial to abiotic stresses moss responses; however, little is known about the moss photosynthesis regulation under nuclide treatment. We measured chlorophyll fluorescence parameters in PSI, photosystem II (PSII) and the P700 redox state, oxidative stress in the moss Racomitrium japonicum under low (5 mg/L), moderate (50 mg/L) and high (500 mg/L) Sr2+ stress level. Moderate and high Sr2+ stress triggered H2O2 and malondialdehyde (MDA) generation, and catalase (CAT) activity increases, which are involved in reactive oxygen species regulation. The significant PSII photochemistry (Fv/Fm), Chla/chlb, Y(I)/Y(II), Y(NA), Y(ND) and ETRI-ETRII decreases at moderate and high Sr2+, and the Y(I), Y(II) decreases at high Sr2+ revealed the photo-inhibition and photo-damage in PSI and PSII by moderate and high Sr2+ stress. The nonphotochemical quenching (NPQ) increased significantly at moderate and high Sr2+ stress, reflecting a heat-dissipation-related photo-protective mechanism in antenna system and reaction centers. Moreover, rapid re-oxidation of P700 indicated that FLV-dependent flows significantly regulated PSI redox state under moderate and high Sr2+ stress. and CEF upregulation was found at low Sr2+. Finally, photosynthetic acclimation to Sr2+ stress in R. japonicum was linked to FLVs and CEF adjustments.

Design, Synthesis and Structure-Activity Relationship Studies of Glycosylated Derivatives of Marine Natural Product Lamellarin D.

Lamellarin D, a marine natural product, acts as a potent inhibitor of DNA topoisomerase I (Topo I). To modify its physicochemical property and biological activity, a series of mono- and di-glycosylated derivatives were designed and synthesized through 22-26 multi-steps. Their inhibition of human Topo I was evaluated, and most of the glycosylated derivatives exhibited high potency in inhibiting Topo I activity as well as lamellarin D. All the 15 target compounds were evaluated for their cytotoxic activities against five human cancer cell lines. The typical lamellarin derivative ZL-3 exhibited the best activity with IC50 values of 3 nM, 10 nM, and 15 nM against human lung cancer A549 cells, human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells. Compound ZL-1 exhibited anti-cancer activity with IC50 of 14 nM and 24 nM against human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells, respectively. Cell cycle analysis in MDA-MB-231 suggested ZL-3 inhibited cell growth through arresting cells at the G2/M phase of the cell cycle. Further tests showed a significant improvement in aqueous solubility of ZL-1 and ZL-7. This study suggested that glycosylation could be utilized as a useful strategy to optimize lamellarin D derivatives as Topo I inhibitors and anticancer agents.

Cofilin-Mediated Actin Stress Response Is Maladaptive in Heat-Stressed Embryos.

Environmental stress threatens the fidelity of embryonic morphogenesis. Heat, for example, is a teratogen. Yet how heat affects morphogenesis is poorly understood. Here, we identify a heat-inducible actin stress response (ASR) in Drosophila embryos that is mediated by the activation of the actin regulator Cofilin. Similar to ASR in adult mammalian cells, heat stress in fly embryos triggers the assembly of intra-nuclear actin rods. Rods measure up to a few microns in length, and their assembly depends on elevated free nuclear actin concentration and Cofilin. Outside the nucleus, heat stress causes Cofilin-dependent destabilization of filamentous actin (F-actin) in actomyosin networks required for morphogenesis. F-actin destabilization increases the chance of morphogenesis mistakes. Blocking the ASR by reducing Cofilin dosage improves the viability of heat-stressed embryos. However, improved viability correlates with restoring F-actin stability, not rescuing morphogenesis. Thus, ASR endangers embryos, perhaps by shifting actin from cytoplasmic filaments to an elevated nuclear pool.

Membrane Supply and Demand Regulates F-Actin in a Cell Surface Reservoir.

Cells store membrane in surface reservoirs of pits and protrusions. These membrane reservoirs facilitate cell shape change and buffer mechanical stress, but we do not know how reservoir dynamics are regulated. During cellularization, the first cytokinesis in Drosophila embryos, a reservoir of microvilli unfolds to fuel cleavage furrow ingression. We find that regulated exocytosis adds membrane to the reservoir before and during unfolding. Dynamic F-actin deforms exocytosed membrane into microvilli. Single microvilli extend and retract in ∼20 s, while the overall reservoir is depleted in sync with furrow ingression over 60-70 min. Using pharmacological and genetic perturbations, we show that exocytosis promotes microvillar F-actin assembly, while furrow ingression controls microvillar F-actin disassembly. Thus, reservoir F-actin and, consequently, reservoir dynamics are regulated by membrane supply from exocytosis and membrane demand from furrow ingression.

The maternal-to-zygotic transition targets actin to promote robustness during morphogenesis.

Robustness is a property built into biological systems to ensure stereotypical outcomes despite fluctuating inputs from gene dosage, biochemical noise, and the environment. During development, robustness safeguards embryos against structural and functional defects. Yet, our understanding of how robustness is achieved in embryos is limited. While much attention has been paid to the role of gene and signaling networks in promoting robust cell fate determination, little has been done to rigorously assay how mechanical processes like morphogenesis are designed to buffer against variable conditions. Here we show that the cell shape changes that drive morphogenesis can be made robust by mechanisms targeting the actin cytoskeleton. We identified two novel members of the Vinculin/α-Catenin Superfamily that work together to promote robustness during Drosophila cellularization, the dramatic tissue-building event that generates the primary epithelium of the embryo. We find that zygotically-expressed Serendipity-α (Sry-α) and maternally-loaded Spitting Image (Spt) share a redundant, actin-regulating activity during cellularization. Spt alone is sufficient for cellularization at an optimal temperature, but both Spt plus Sry-α are required at high temperature and when actin assembly is compromised by genetic perturbation. Our results offer a clear example of how the maternal and zygotic genomes interact to promote the robustness of early developmental events. Specifically, the Spt and Sry-α collaboration is informative when it comes to genes that show both a maternal and zygotic requirement during a given morphogenetic process. For the cellularization of Drosophilids, Sry-α and its expression profile may represent a genetic adaptive trait with the sole purpose of making this extreme event more reliable. Since all morphogenesis depends on cytoskeletal remodeling, both in embryos and adults, we suggest that robustness-promoting mechanisms aimed at actin could be effective at all life stages.