The Effect of Growth and Measurement Temperature on the Activity of the Alternative Respiratory Pathway

A postulated role of the CN-resistant alternative respiratory pathway in plants is the maintenance of mitochondrial electron transport at low temperatures that would otherwise inhibit the main phosphorylating pathway and prevent the formation of toxic reactive oxygen species. This role is supported by the observation that alternative oxidase protein levels often increase when plants are subjected to growth at low temperatures. We used oxygen isotope fractionation to measure the distribution of electrons between the main and alternative pathways in mung bean (Vigna radiata) and soybean (Glycine max) following growth at low temperature. The amount of alternative oxidase protein in mung bean grown at 19°C increased over 2-fold in both hypocotyls and leaves compared with plants grown at 28°C but was unchanged in soybean cotyledons grown at 14°C compared with plants grown at 28°C. When the short-term response of tissue respiration was measured over the temperature range of 35°C to 9°C, decreases in the activities of both main and alternative pathway respiration were observed regardless of the growth temperature, and the relative partitioning of electrons to the alternative pathway generally decreased as the temperature was lowered. However, cold-grown mung bean plants that up-regulated the level of alternative oxidase protein maintained a greater electron partitioning to the alternative oxidase when measured at temperatures below 19°C supporting a role for the alternative pathway in response to low temperatures in mung bean. This response was not observed in soybean cotyledons, in which high levels of alternative pathway activity were seen at both high and low temperatures.     

Many chronological aging clocks can be found throughout the epigenome: Implications for quantifying biological aging

Epigenetic alterations are a hallmark of aging and age‐related diseases. Computational models using DNA methylation data can create “epigenetic clocks” which are proposed to reflect “biological” aging. Thus, it is important to understand the relationship between predictive clock sites and aging biology. To do this, we examined over 450,000 methylation sites from 9,699 samples. We found ~20% of the measured genomic cytosines can be used to make many different epigenetic clocks whose age prediction performance surpasses that of telomere length. Of these predictive sites, the average methylation change over a lifetime was small (~1.5%) and these sites were under‐represented in canonical regions of epigenetic regulation. There was only a weak association between “accelerated” epigenetic aging and disease. We also compare tissue‐specific and pan‐tissue clock performance. This is critical to applying clocks both to new sample sets in basic research, as well as understanding if clinically available tissues will be feasible samples to evaluate “epigenetic aging” in unavailable tissues (e.g., brain). Despite the reproducible and accurate age predictions from DNA methylation data, these findings suggest they may have limited utility as currently designed in understanding the molecular biology of aging and may not be suitable as surrogate endpoints in studies of anti‐aging interventions. Purpose‐built clocks for specific tissues age ranges or phenotypes may perform better for their specific purpose. However, if purpose‐built clocks are necessary for meaningful predictions, then the utility of clocks and their application in the field needs to be considered in that context.     

Dll4-Notch Signalling Blockade Synergizes Combined Ultrasound-Stimulated Microbubble and Radiation Therapy in Human Colon Cancer Xenografts

Tumour vasculature acts as an essential lifeline for tumour progression and facilitates metastatic spread. Novel vascular targeting strategies aiming to sustain vascular shutdown could potentially induce substantial damage, resulting in a significant tumour growth delay. We investigated the combination of two novel complementary vascular targeting agents with radiation therapy in a strategy aiming to sustain vascular disruption. Experiments were carried out with delta-like ligand 4 (Dll4) blockade (angiogenesis deregulator) treatment administered in combination with a radiation-based vascular destruction treatment in a highly aggressive well-perfused colon cancer tumour line implanted in female athymic nude mice. Tumours were treated with permutations of radiation, ultrasound-stimulated microbubbles (USMB) and Dll4 monoclonal antibody (mAb). Tumour vascular response was assessed with three-dimensional power Doppler ultrasound to measure active flow and immunohistochemistry. Tumour response was assessed with histochemical assays and longitudinal measurements of tumour volume. Our results suggest a significant tumour response in animals treated with USMB combined with radiation, and Dll4 mAb, leading to a synergistic tumour growth delay of up to 24 days. This is likely linked to rapid cell death within the tumour and a sustained tumour vascular shutdown. We conclude that the triple combination treatments cause a vascular shutdown followed by a sustained inhibition of angiogenesis and tumour cell death, leading to a rapid tumour vascular-based ‘collapse’ and a significant tumour growth delay.     

Liposome-mediated uptake of chloroplasts by plant protoplasts

Summary Liposomes, artificial lipid vesicles, have been used to induce the uptake of isolated spinach chloroplasts into protoplasts of bothNeurospora crassa andDatura innoxia. Chloroplasts showed high oxygen evolution rates preceding uptake and for extended periods of time after uptake. Survival, as measured by pigment retention and oxygen evolution, was much improved over polyethylene glycol induce uptake. Possible future application of liposome-mediated uptake in plant protoplast studies are discussed.     

Relative effect of taphonomy on calcification temperature estimates from fossil planktonic foraminifera

This paper explores the effects of preservation and taphonomy on the ultrastructure of recent and fossil (Quaternary and Neogene) Globigerinoides using scanning electron microscopy and thin section petrography. We show preservation states from: pristine (plankton tow) specimens that are “glassy”, have a microcrystalline test structure, and bear sharply defined interpore ridges with delicate spines; through core top and fossil specimens that have gametogenic calcite veneers of euhedral or lumpy deposits covering the interpore ridges and spine bases; to fossil material with extensive dissolution of the test wall and diagenetic calcite formed during shallow burial (less than 300 m below the sea floor). The latter produce a “grainy” texture to the test. Although we cannot unravel the precise effects of ecology and taphonomy on calcification temperature at every site, we show that for well-preserved fossil material with gametogenic calcite, temperature estimates are typically 2-3 °C cooler than modern sea surface, and are similar to those recorded using the δ¹⁸O of core top material from tropical latitudes. In contrast, at tropical sites with poor fossil preservation, estimates of calcification temperature are significantly cooler, sometimes by more than 10 °C than expected from present observations.     

In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer

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