Slowing down translation in either the cytosol or the mitochondria is a conserved longevity mechanism. Here, we found a non-interventional natural correlation of mitochondrial and cytosolic ribosomal ...proteins (RPs) in mouse population genetics, suggesting a translational balance. Inhibiting mitochondrial translation in C. elegans through mrps-5 RNAi repressed cytosolic translation. Transcriptomics integrated with proteomics revealed that this inhibition specifically reduced translational efficiency of mRNAs required in growth pathways while increasing stress response mRNAs. The repression of cytosolic translation and extension of lifespan from mrps-5 RNAi were dependent on atf-5/ATF4 and independent from metabolic phenotypes. We found the translational balance to be conserved in mammalian cells upon inhibiting mitochondrial translation pharmacologically with doxycycline. Lastly, extending this in vivo, doxycycline repressed cytosolic translation in the livers of germ-free mice. These data demonstrate that inhibiting mitochondrial translation initiates an atf-5/ATF4-dependent cascade leading to coordinated repression of cytosolic translation, which could be targeted to promote longevity.
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•Mitochondrial and cytosolic ribosomal proteins are balanced with a natural ratio•Blocking mitochondrial ribosomes in worms and mice reduces cytosolic translation•Translational balance is ATF4/atf-5-dependent and conserved in human cells•atf-5-induced translational repression is independent from mitochondrial bioenergetics
Molenaars, Janssens, and colleagues report on a natural balance between cytosolic and mitochondrial ribosomal proteins, driven by an active link between two longevity pathways. They demonstrate that the inhibition of mitochondrial translation regulates cytosolic translation via the transcription factor Atf4/atf-5, a phenomenon conserved in worms, human cells, and in vivo in mice.
Deregulated global mRNA translation is an emerging feature of cancer cells. Oncogenic transformation in colorectal cancer (CRC) is driven by mutations in APC, KRAS, SMAD4, and TP53, known as the ...adenoma-carcinoma sequence (ACS). Here we introduce each of these driver mutations into intestinal organoids to show that they are modulators of global translational capacity in intestinal epithelial cells. Increased global translation resulting from loss of Apc expression was potentiated by the presence of oncogenic KrasG12D
. Knockdown of Smad4 further enhanced global translation efficiency and was associated with a lower 4E-BP1-to-eIF4E ratio. Quadruple mutant cells with additional P53 loss displayed the highest global translational capacity, paralleled by high proliferation and growth rates, indicating that the proteome is heavily geared toward cell division. Transcriptional reprogramming facilitating global translation included elevated ribogenesis and activation of mTORC1 signaling. Accordingly, interfering with the mTORC1/4E-BP/eIF4E axis inhibited the growth potential endowed by accumulation of multiple drivers. In conclusion, the ACS is characterized by a strongly altered global translational landscape in epithelial cells, exposing a therapeutic potential for direct targeting of the translational apparatus.
This paper investigates the durability of geopolymers and geopolymeric mortars made with metakaolin and alkaline activators, with and without a coconut fiber addition, after immersion for seven days ...into solutions of citric acid (1%, 2.5%, 5%, and 10%); hydrochloric acid (1%, 2.5%, 5%, and 10%); and sulfuric acid (1%, 2.5%, 5%, and 10%). The study focuses on mass changes, uniaxial compressive strength, flexural strength, and ultrasound pulse velocity measurements. X-ray diffraction and scanning electron microscopy are used to analyze the degradation products and microstructural changes. The aim is to assess the effect of acid exposure on the strength and stability of geopolymer materials and identify any protective effects of coconut fiber reinforcement. The samples are immersed in acid solutions of varying concentrations, and their mechanical properties are measured. The presence of coconut fibers slightly modifies the physical properties and the compressive strength, improving the mechanical flexural strength. Geopolymer and geopolymeric mortar materials experienced a weak decrease in strength when exposed to solutions of citric acid and a significant one when exposed to solutions of hydrochloric and sulfuric acids, attributed to depolymerization of the aluminosilicate binders. Brick waste geopolymeric mortars reinforced with coconut fibers showed the best performance in acid solutions with respect to geopolymers and quartz-rich sand geopolymeric mortars, suggesting a more stable cross-linked aluminosilicate geopolymer structure in this material.
The quarrying of marble and its processing to produce building materials often generates a negative impact on the environment. In the Apuan Alps marble district, a renowned quarrying area in Italy ...since ancient times, the aquatic pollution of water bodies, caused by the presence of marble waste in the form of powder or sludge, represents a significant and current environmental problem. Depending on the different national and international regulations on waste management, the marble waste can be classified as a special non-hazardous industrial waste. If marble waste has been managed according to environmental international and national laws, it can be reused as a by-product. For this, the present work aims to evaluate the reuse of marble waste as a material in replacement for cement for producing mortars. Subsequently, the mechanical and physical tests were carried out to evaluate the specific properties of the obtained materials during and after the curing time. The results showed that replacement of cement into mortars by marble waste always causes a decrease of mechanical properties, with still acceptable values for many applications up to a substitution of less than 25%. From the collected data, the use of marble waste in the production of cement mortars represents an adequate and sustainable destination of this by-product.
Natural or artificial light allows us to see and analyze matter with our eyes, which are the first tools used in several experiments. In geosciences, particularly in mineralogy, light is used for ...optical microscopy observations. Reflected and transmitted light applied to the study of ore deposits can be useful to discriminate between gangue from precious phases. Knowledge of the structural and morphological characteristics, combined with the quantitative evaluation of mineral abundance, is fundamental for determining the grade of ore deposits. The accuracy and reliability of the information are closely linked to the ability of the mineralogist, who more and more often uses Scanning Electron technology and automated mineralogy systems to validate the observations or solve complex mineralogy. While highly accurate, these methods are often prohibitively expensive. The use of image analysis using standard algorithms and artificial intelligence, available as open source, and commercial packages (such as ImageJ, Fiji or MATLAB), can provide advantages in fast, cost-effective, and robust mineral analysis. Recently, the application of neural networks provided increasingly effective image analysis and, among the different types of neural networks available today, the self-organizing maps of Kohonen (SOM) seem to be among the most promising, given their capacity to receive many images as inputs and reduce them to a low number of neuronal outputs that represent all the input characteristics in a lower-dimensional space. In this work, we will show the preliminary results of a new method based on SOM and the combined use of images acquired in transmitted and reflected light to reconstruct false 3D surfaces, which were able to show the presence of intergrow between gangue phases and precious minerals.
A multidisciplinary approach combining multiscale geological-structural analyses (from field to microscale) and clay mineral transformations (clay mineralogy, illite and chlorite “crystallinity” and ...b cell dimension (
b
0
) of K-white mica) was adopted to unravel the tectono-metamorphic evolution of low- and very low-grade tectono-metamorphic units from the Intra-Pontide suture zone in northern Turkey. The mineralogical study allowed to better evaluate the structural stacking outlined during the geological mapping, leading to distinguish three tectono-metamorphic units, two in epizone (Daday and Emirköy units) and one in anchizone (Çifter Unit) metamorphic conditions. The mesostructural and microstructural analyses suggest a polyphase tectonic-metamorphic evolution. The different macroscopic features observed between the two units characterized by the same epizone metamorphism, can be justified by the evidence that these metamorphic conditions were acquired during the last stages of exhumation in the Daday Unit, while they constrained the metamorphic-peak conditions in the Emirköy Unit. Contemporary analyses and comparison between structural and mineralogical data have thus proven to be a powerful tool to investigate the low-grade and very low-grade metamorphic environments, allowing at the same time to solve the apparent contradictions deriving from the mineralogical study and to significantly improve the detail of the geological mapping in the field.
This paper presents the results obtained from the thermal analysis of a set of geomaterials (clays, pyroclastic materials, and industrial recycled materials) to be used as raw materials for the ...synthesis of geopolymers, specifically designed for the conservation of Cultural Heritage (CH) buildings, particularly in seismic hazard zones such as Sicily. X-ray diffraction and gas volumetric analysis (calcimetry) were applied to this set of raw materials in order to characterize the materials from the chemical and structural point of view. Thermogravimetric analysis (TG), TG coupled to Fourier transform infrared spectroscopy (TG-FTIR), and differential scanning calorimetry were used to characterize their thermal behavior. The statistical treatment of the thermogravimetric data by principal component analysis and hierarchical clustering analysis highlights the direct relation between the thermal data and the material composition that will be exploited for the selection of the best materials to obtain geopolymers specifically designed for the conservation of CH buildings.
Abstract
Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene ...variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5′UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80S monosome reduction, the downstream effects are remarkably different. Cells carrying the 5′UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5′UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts.
Soluble salts are compounds found inside ornamental rocks and building stones exposed to atmospheric agents in environments rich in alkaline metal ions, such as sodium and potassium. The damage ...induced by their crystallization in those materials, used to build monuments and architectural structures of great importance, is an unsolved problem. Sodium sulfate is one of the most common and harmful salt found in these constructions. In this work, we studied the resistance through time to the wet-drying cycles of some natural stones (calcarenites, marbles, and sandstones) that have been utilized in the historical architecture in Italy. Samples were freshly cut and thermally aged to simulate increasing decay. Induced porosity in the thermally degraded samples was high in calcarenites, medium in marbles, and low in sandstones. Specimens subjected to artificial thermal aging lost a major percentage of mass compared to the non-weathered ones, when affected by the crystallization of soluble salts. With this study, we have observed that samples subjected to different wetting and drying cycles degrade faster due to the action of soluble salts, compared to samples that are not subjected to these cycles.
This study presents the petrographic and chemical characterization of the frescoes in the Church of San Panfilo in Tornimparte (AQ, Italy) by Saturnino Gatti, a prominent painter of the late ...15th–early 16th century, known for his exquisite technique, composition, and use of color. The characterization of the frescoes is essential for understanding the materials and techniques used by Gatti, as well as for identifying the stratigraphy and painting phases. Eighteen samples were collected from the original paint layers, later additions (17th century), and restored surfaces, and analyzed by optical microscopy, cathodoluminescence microscopy, scanning electron microscopy (SEM-EDS), μ-Raman, and electron paramagnetic resonance (EPR). The analyses revealed a microstratigraphy often made of three main layers: (1) preparation, consisting of lime plaster and sand; (2) pigmented lime, applied by the fresco technique; and (3) additional pigmented layer on the surface. The most often recurring pigments are black, red, yellow (all generally linked with the fresco technique), and blue (applied “a secco”). The presence of two painting phases was also noted in one sample, probably resulting from a rethinking or restoration. These findings contribute to the understanding of the history and past restoration works of this cultural heritage site, providing important insights not only for conservators and restorers, but also for a broader understanding of Italian fresco painting and art history of the late 15th and early 16th centuries.
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