Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws ...relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly-complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.
Shade caused by the proximity of neighboring vegetation triggers a set of acclimation responses to either avoid or tolerate shade. Comparative analyses between the shade‐avoider Arabidopsis thaliana ...and the shade‐tolerant Cardamine hirsuta revealed a role for the atypical basic‐helix‐loop‐helix LONG HYPOCOTYL IN FR 1 (HFR1) in maintaining the shade tolerance in C. hirsuta, inhibiting hypocotyl elongation in shade and constraining expression profile of shade‐induced genes. We showed that C. hirsuta HFR1 protein is more stable than its A. thaliana counterpart, likely due to its lower binding affinity to CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), contributing to enhance its biological activity. The enhanced HFR1 total activity is accompanied by an attenuated PHYTOCHROME INTERACTING FACTOR (PIF) activity in C. hirsuta. As a result, the PIF‐HFR1 module is differently balanced, causing a reduced PIF activity and attenuating other PIF‐mediated responses such as warm temperature‐induced hypocotyl elongation (thermomorphogenesis) and dark‐induced senescence. By this mechanism and that of the already‐known of phytochrome A photoreceptor, plants might ensure to properly adapt and thrive in habitats with disparate light amounts.
Synopsis
Plant shade triggers distinct acclimation responses in neighboring vegetation. Here, comparison of shade‐avoiding Arabidopsis thaliana and shade‐tolerant Cardamine hirsuta reveals that enhanced repressor activity of the photomorphogenesis regulator HFR1 promotes shade tolerance in C. hirsuta via regulation of the transcription factor PIF7.
HFR1 activity is enhanced and PIF7 activity attenuated in C. hirsuta compared to A. thaliana.
Cardamine hirsuta HFR1 protein is more stable than its A. thaliana counterpart.
Cardamine hirsuta HFR1 has lower binding affinity to COP1, which contributes to enhance its biological activity.
Other PIF‐mediated growth responses, such as temperature‐induced hypocotyl elongation and dark‐induced senescence, are attenuated in C. hirsuta.
Modulation of the stability and COP1 interaction of the photomorphogenesis regulator HFR1 regulates shade tolerance differences in Arabidopsis and C. hirsuta seedlings.
Perception of vegetation proximity or plant shade informs of potential competition for resources by the neighboring vegetation. As vegetation proximity impacts on both light quantity and quality, ...perception of this cue by plant photoreceptors reprograms development to result in responses that allow plants to compete with the neighboring vegetation. Developmental reprogramming involves massive and rapid changes in gene expression, with the concerted action of photoreceptors and downstream transcription factors. Changes in gene expression can be modulated by epigenetic processes that alter chromatin compaction, influencing the accessibility and binding of transcription factors to regulatory elements in the DNA. However, little is known about the epigenetic regulation of plant responses to the proximity of other plants. In this manuscript, we review what is known about plant shade effects on chromatin changes at the cytological level, that is, changes in nuclear morphology and high order chromatin density. We address which are the specific histone post‐transcriptional modifications that have been associated with changes in shade‐regulated gene expression, such as histone acetylation and histone methylation. Furthermore, we explore the possible mechanisms that integrate shade signaling components and chromatin remodelers to settle epigenetic marks at specific loci. This review aims to be a starting point to understand how a specific environmental cue, plant shade, integrates with chromatin dynamics to implement the proper acclimation responses.
Realisation of experiments even on small and medium-scale quantum computers requires an optimisation of several parameters to achieve high-fidelity operations. As the size of the quantum register ...increases, the characterisation of quantum states becomes more difficult since the number of parameters to be measured grows as well and finding efficient observables in order to estimate the parameters of the model becomes a crucial task. Here we propose a method relying on application of Bayesian inference that can be used to determine systematic, unknown phase shifts of multi-qubit states. This method offers important advantages as compared to Ramsey-type protocols. First, application of Bayesian inference allows the selection of an adaptive basis for the measurements which yields the optimal amount of information about the phase shifts of the state. Secondly, this method can process the outcomes of different observables at the same time. This leads to a substantial decrease in the resources needed for the estimation of phases, speeding up the state characterisation and optimisation in experimental implementations. The proposed Bayesian inference method can be applied in various physical platforms that are currently used as quantum processors.
Objective
Phosphomannomutase deficiency (PMM2 congenital disorder of glycosylation PMM2‐CDG) causes cerebellar syndrome and strokelike episodes (SLEs). SLEs are also described in patients with ...gain‐of‐function mutations in the CaV2.1 channel, for which acetazolamide therapy is suggested. Impairment in N‐glycosylation of CaV2.1 promotes gain‐of‐function effects and may participate in cerebellar syndrome in PMM2‐CDG. AZATAX was designed to establish whether acetazolamide is safe and improves cerebellar syndrome in PMM2‐CDG.
Methods
A clinical trial included PMM2‐CDG patients, with a 6‐month first‐phase single acetazolamide therapy group, followed by a randomized 5‐week withdrawal phase. Safety was assessed. The primary outcome measure was improvement in the International Cooperative Ataxia Rating Scale (ICARS). Other measures were the Nijmegen Pediatric CDG Rating Scale (NPCRS), a syllable repetition test (PATA test), and cognitive scores.
Results
Twenty‐four patients (mean age = 12.3 ± 4.5 years) were included, showing no serious adverse events. Thirteen patients required dose adjustment due to low bicarbonate or asthenia. There were improvements on ICARS (34.9 ± 23.2 vs 40.7 ± 24.8, effect size = 1.48, 95% confidence interval CI = 4.0–7.6, p < 0.001), detected at 6 weeks in 18 patients among the 20 responders, on NPCRS (95% CI = 0.3–1.6, p = 0.013) and on the PATA test (95% CI = 0.5–3.0, p = 0.006). Acetazolamide improved prothrombin time, factor X, and antithrombin. Clinical severity, epilepsy, and lipodystrophy predicted greater response. The randomized withdrawal phase showed ICARS worsening in the withdrawal group (effect size = 1.46, 95% CI = 2.65–7.52, p = 0.001).
Interpretation
AZATAX is the first clinical trial of PMM2‐CDG. Acetazolamide is well tolerated and effective for motor cerebellar syndrome. Its ability to prevent SLEs and its long‐term effects on kidney function should be addressed in future studies. Ann Neurol 2019;85:740–751
A Tepary bean lectin fraction (TBLF) has been studied because it exhibits differential cytotoxic and anticancer effects on colon cancer. The present work focuses on the evaluation of the apoptotic ...mechanism of action on colon cancer cells. Initially, lethal concentrations (LC
) were obtained for the three studied cell lines (HT-29, RKO and SW-480). HT-29 showed the highest LC
, 10 and 100 times higher than that of RKO and SW-480 cells, respectively. Apoptosis was evaluated by flow cytometry, where HT-29 cells showed the highest levels of early and total apoptosis, caspases activity was confirmed and necrosis was discarded. The effect on cell cycle arrest was shown in the G0/G1 phase. Specific apoptosis-related gene expression was determined, where an increase in p53 and a decrease in Bcl-2 were observed. Expression of p53 gene showed the maximum level at 8 h with an important decrease at 12 and 24 h, also the phosphorylated p53(ser46) increased at 8 h. Our results show that TBLF induces apoptosis in colon cancer cells by p-p53(ser46) involvement. Further studies will focus on studying the specific signal transduction pathway.
We have studied the possible use of soybean meal (SM) in sharpsnout seabream diets by progressively increasing its inclusion level (0%, 20%, 40% and 60%) at the expense of fish meal in isonitrogenous ...(45%) and isoenergetic formulated (20 MJ/kg) diets. Fish of two different sizes (48 g and 195 g of initial weight) were kept in seawater tanks (26 °C on average) and fed to satiety until they reached a weight of 118 g and 340 g, after 64 and 91 days respectively. Feed consumption increased along with the soybean meal content of the diet, the differences becoming statistically significant in smaller animals as from 40% of inclusion. In larger animals, the diet containing the highest level of soybean meal produced the lowest final weight. As the soybean meal content increased, feeding efficiency and protein utilization of the diet decreased, an effect probably due to the smaller digestibility coefficient observed for these diets. Based on the results of the sensory test, flesh quality was very little affected, albeit fish feeding on diets with partial replacement of fish meal tended to be somewhat softer. Despite extending the fattening period required to reach the same final weight, the economic analysis indicates that inclusion of soybean meal in the diet reduces feeding costs.
Residual soil pollution from the Aznalcóllar mine spill is still a problem in some parts of the affected area, today converted in the Guadiamar Green Corridor. Dispersed spots of polluted soils, ...identified by the absence of vegetation, are characterized by soil acid pH and high concentrations of As, Pb, Cu and Zn. Ex situ remediation techniques were performed with unrecovered soil samples. Landfarming, Composting and Biopiles techniques were tested in order to immobilize pollutants, to improve soil properties and to promote vegetation recovery. The effectiveness of these techniques was assessed by toxicity bioassays: Lactuca sativa L. root elongation test, Vibrio fischeri bioluminescence reduction test, soil induced respiration test, and Eisenia andrei survival and metal bioaccumulation tests. Landfarming and Composting were not effective techniques, mainly due to the poor improvement of soil properties which maintained high soluble concentrations of Zn and Cu after treatments. Biopile technique, using adjacent recovered soils in the area, was the most effective action in the reduction of soil toxicity; the improvement of soil properties and the reduction in pollutants solubility were key to improve the response of the tested organisms. Therefore, the mixture of recovered soils with polluted soils in the areas affected by residual contamination is considered a more suitable technique to reduce the residual pollution and to promote the complete soil recovery in the Guadiamar Green Corridor.
•Residual soil pollution in Guadiamar Green Corridor is still a problem 18 years after contamination.•Soil toxicity bioassays were key tools for the assessment of remediation techniques applied.•Landfarming and Composting were not effective due to the high soluble concentrations of Zn and Cu after treatment.•Biopiles, using recovered soils in the area, were the most effective treatment for soil remediation.
Lignocellulose is the most abundant biopolymer in the biosphere. It is inexpensive and therefore considered an attractive feedstock to produce biofuels and other biochemicals. Thermochemical and/or ...enzymatic pretreatment is used to release fermentable monomeric sugars. However, a variety of inhibitory by‐products such as weak acids, furans, and phenolics that inhibit cell growth and fermentation are also released. Phenolic compounds are among the most toxic components in lignocellulosic hydrolysates and slurries derived from lignin decomposition, affecting overall fermentation processes and production yields and productivity. Ligninolytic enzymes have been shown to lower inhibitor concentrations in these hydrolysates, thereby enhancing their fermentability into valuable products. Among them, laccases, which are capable of oxidizing lignin and a variety of phenolic compounds in an environmentally benign manner, have been used for biomass delignification and detoxification of lignocellulose hydrolysates with promising results. This review discusses the state of the art of different enzymatic approaches to hydrolysate detoxification. In particular, laccases are used in separate or in situ detoxification steps, namely in free enzyme processes or immobilized by cell surface display technology to improve the efficiency of the fermentative process and consequently the production of second‐generation biofuels and bio‐based chemicals.
PDF
![Association between [18F]fl...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0007-1323_1365-2168/small "Association between [18F]fluorodeoxyglucose uptake and prognostic parameters in breast cancer")
