SciCombinator

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Liver kinase B1 (LKB1) is a tumor suppressor gene whose inactivation is frequent in different tumor types, especially in lung adenocarcinoma (about 30% of cases). LKB1 has an essential role in the control of cellular redox homeostasis by regulating ROS production and detoxification. Loss of LKB1 makes the tumor cell more sensitive to oxidative stress and consequently to stress-inducing treatments, such as chemotherapy and radiotherapy. LKB1 loss triggers complex changes in tumor microenvironment, supporting a role in the regulation of angiogenesis and suggesting a potential role in the response to anti-angiogenic treatment. On the other hand, LKB1 deficiency can promote an immunosuppressive microenvironment and may be involved in primary resistance to anti-PD-1/anti-PD-L1, as it has been reported in lung cancer. The aim of this review is to discuss interactions of LKB1 with the tumor microenvironment and the potential applications of this knowledge in predicting response to treatment in lung cancer.

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In the last three decades, many giant DNA viruses have been discovered. Giant viruses present a unique and essential research frontier for studies of self-assembly and regulation of supramolecular assemblies. The question on how these giant DNA viruses assemble thousands of proteins so accurately to form their protein shells, the capsids, remains largely unanswered. Revealing the mechanisms of giant virus assembly will help to discover the mysteries of many self-assembly biology problems. Paramecium bursaria Chlorella virus-1 (PBCV-1) is one of the most intensively studied giant viruses. Here, we implemented a multi-scale approach to investigate the interactions among PBCV-1 capsid building units called capsomers. Three binding modes with different strengths are found between capsomers around the relatively flat area of the virion surface at the icosahedral 2-fold axis. Furthermore, a capsomer structure manipulation package is developed to simulate the capsid assembly process. Using these tools, binding forces among capsomers were investigated and binding funnels were observed that were consistent with the final assembled capsid. In addition, total binding free energies of each binding mode were calculated. The results helped to explain previous experimental observations. Results and tools generated in this work established an initial computational approach to answer current unresolved questions regarding giant virus assembly mechanisms. Results will pave the way for studying more complicated process in other biomolecular structures.

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Although HIV-1 subtype A has predominated in Russia since the end of the 20th century, other viral variants also circulate in this country. The dramatic outbreak of HIV-1 subtype G in 1988-1990 represents the origin of this variant spreading in Russia. However, full genome sequencing of the nosocomial viral variant and an analysis of the current circulating variants have not been conducted. We performed near full-length genome sequencing and phylogenetic and recombination analyses of 11 samples; the samples were determined to be subtype G based on an analysis of the pol region. Three samples were reliably obtained from patients infected during the nosocomial outbreak. The other 8 samples were obtained from patients who were diagnosed in 2010-2015. Phylogenetic analysis confirmed that a man from the Democratic Republic of the Congo was the origin of the outbreak. We also found that currently circulating viral variants that were genotyped as subtype G according to their pol region are in fact unique recombinant forms. These recombinant forms are similar to the BG-recombinants from Western Europe, particularly Spain and Portugal. The limitations of subtyping based on the pol region suggest that these viral variants are more widespread in Europe than is currently supposed.

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In vitro maturation of cardiomyocytes in 3D is essential for the development of viable cardiac models for therapeutic and developmental studies. The method by which cardiomyocytes undergoes maturation has significant implications for understanding cardiomyocytes biology. The regulation of the extracellular matrix (ECM) by changing the composition and stiffness is quintessential for engineering a suitable environment for cardiomyocytes maturation. In this paper, we demonstrate that collagen type I, a component of the ECM, plays a crucial role in the maturation of cardiomyocytes. To this end, embryonic stem-cell derived cardiomyocytes were incorporated into Matrigel-based hydrogels with varying collagen type I concentrations of 0 mg, 3 mg, and 6 mg. Each hydrogel was analyzed by measuring the degree of stiffness, the expression levels of MLC2v, TBX18, and pre-miR-21, and the size of the hydrogels. It was shown that among the hydrogel variants, the Matrigel-based hydrogel with 3 mg of collagen type I facilitates cardiomyocyte maturation by increasing MLC2v expression. The treatment of transforming growth factor β1 (TGF-β1) or fibroblast growth factor 4 (FGF-4) on the hydrogels further enhanced the MLC2v expression and thereby cardiomyocyte maturation.

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Demand side interventions, such as dietary change, can significantly contribute towards the achievement of 2030 national sustainable development goals. However, most previous studies analysing the consequences of dietary change focus on a single dimension of sustainability (e.g., environment) using a limited number of indicators and dietary scenarios. A multi-dimension and multi-indicator analysis can identify the potential trade-offs. Here, starting from the current food consumption data (year 2011), we first designed nine alternative dietary scenarios (healthy Swiss diet, healthy global diet, vegetarian, vegan, pescatarian, flexitarian, protein-oriented and meat-oriented diets and a food greenhouse gas tax diet). Next we calculated three nutritional quality (nutrient balance score, disqualifying nutrient score, percent population with adequate nutrition), five environmental (greenhouse gas, water, land, nitrogen and phosphorus use), one economic (daily food expenditure) and one human health indicator (DALYs) for current and alternative diets. We found that transition towards a healthy diet following the guidelines of Swiss society of nutrition is the most sustainable option and is projected to result in 36% lesser environmental footprint, 33% lesser expenditure and 2.67% lower adverse health outcome (DALYs) compared with the current diet. On the other extreme, transition towards a meat or protein oriented diet can lead to large increases in diet related adverse health outcomes, environmental footprint, daily food expenditure and a reduction in intakes of essential nutrients (for Vitamin C, Fibre, Potassium and Calcium). We found that shifting to the vegetarian and vegan diet scenarios might lead to a reduction in intakes of certain micronutrients currently supplied primarily by animal-sourced foods (Vitamin B12, Choline and Calcium). Results show that achieving a sustainable diet would entail a high reduction in the intake of meat and vegetable oils and a moderate reduction in cereals, roots and fish products and at the same time increased intake of legumes, nuts, seeds, fruits and vegetables. We identify several current data and research gaps that need to be filled in order to get more accurate results. Overall, our analysis underscores the need to consider multiple indicators while assessing the dietary sustainability and provides a template to conduct such studies in other countries and settings. Future efforts should focus on assessing the potential of different interventions and policies that can help transition the population from current to sustainable dietary patterns.

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Early childhood is characterised by high physiological iron demand to support processes including blood volume expansion, brain development and tissue growth. Iron is also required for other essential functions including the generation of effective immune responses. Adequate iron status is therefore a prerequisite for optimal child development, yet nutritional iron deficiency and inflammation-related iron restriction are widespread amongst young children in low- and middle-income countries (LMICs), meaning iron demands are frequently not met. Consequently, therapeutic iron interventions are commonly recommended. However, iron also influences infection pathogenesis: iron deficiency reduces the risk of malaria, while therapeutic iron may increase susceptibility to malaria, respiratory and gastrointestinal infections, besides reshaping the intestinal microbiome. This means caution should be employed in administering iron interventions to young children in LMIC settings with high infection burdens. In this narrative review, we first examine demand and supply of iron during early childhood, in relation to the molecular understanding of systemic iron control. We then evaluate the importance of iron for distinct aspects of physiology and development, particularly focusing on young LMIC children. We finally discuss the implications and potential for interventions aimed at improving iron status whilst minimising infection-related risks in such settings. Optimal iron intervention strategies will likely need to be individually or setting-specifically adapted according to iron deficiency, inflammation status and infection risk, while maximising iron bioavailability and considering the trade-offs between benefits and risks for different aspects of physiology. The effectiveness of alternative approaches not centred around nutritional iron interventions for children should also be thoroughly evaluated: these include direct targeting of common causes of infection/inflammation, and maternal iron administration during pregnancy.

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The effective monitoring and maintenance of power lines are becoming increasingly important due to a global growing dependence on electricity. The costs and risks associated with the traditional foot patrol and helicopter-based inspections can be reduced by using UAVs with the appropriate sensors. However, this implies developing algorithms to make the power line inspection process reliable and autonomous. In order to overcome the limitations of visual methods in the presence of poor light and noisy backgrounds, we propose to address the problem of power line detection and modeling based on LiDAR. The PL 2 DM, Power Line LiDAR-based Detection and Modeling, is a novel approach to detect power lines. Its basis is a scan-by-scan adaptive neighbor minimalist comparison for all the points in a point cloud. The power line final model is obtained by matching and grouping several line segments, using their collinearity properties. Horizontally, the power lines are modeled as a straight line, and vertically as a catenary curve. Using a real dataset, the algorithm showed promising results both in terms of outputs and processing time, adding real-time object-based perception capabilities for other layers of processing.

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Several families of polymers possessing various end-groups are characterized by ion mobility mass spectrometry (IMMS). A significant contribution of the end-groups to the ion collision cross section (CCS) is observed, although their role is neglected in current fitting models described in literature. Comparing polymers prepared from different synthetic procedures might thus, be misleading with the current theoretical treatments. We show that this issue is alleviated by comparing the CCS of various polymer ions (polyesters and polyethers) as a function of the number of atoms in the macroion instead of the usual representation involving the degree of polymerization. Finally, we extract the atom number density from the spectra which gives us the possibility to evaluate the compaction of polymer ions, and by extension to discern isomeric polymers.

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Coarctation of the aorta is a form of left ventricular outflow tract obstruction in paediatric patients that can be presented with either bicuspid (BAV) or normal tricuspid (TAV) aortic valve. The congenital BAV is associated with hemodynamic changes and can therefore trigger different molecular remodelling in the coarctation area. This study investigated the proteomic and phosphoproteomic changes associated with BAV for the first time in neonatal coarctation patients. Aortic tissue was collected just proximal to the coarctation site from 23 neonates (BAV; n = 10, TAV; n = 13) that were matched for age (age range 4-22 days). Tissue from half of the patients was frozen and used for proteomic and phosphoproteomic analysis whilst the remaining tissue was formalin fixed and used for analysis of elastin content using Elastic Van-Gieson (EVG) staining. A total of 1796 protein and 75 phosphoprotein accession numbers were detected, of which 34 proteins and one phosphoprotein (SSH3) were differentially expressed in BAV patients compared to TAV patients. Ingenuity Pathway Analysis identified the formation of elastin fibres as a significantly enriched function (p = 1.12 × 10-4) due to the upregulation of EMILIN-1 and the downregulation of TNXB. Analysis of paraffin sections stained with EVG demonstrated increased elastin content in BAV patients. The proteomic/phosphoproteomic analysis also suggested changes in inositol signalling pathways and reduced expression of the antioxidant SOD3. This work demonstrates for the first time that coarcted aortic tissue in neonatal BAV patients has an altered proteome/phosphoproteome consistent with observed structural vascular changes when compared to TAV patients.

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Carbon dots (CDs), a class of carbon-based sub-ten-nanometer nanoparticles, have attracted great attention since their discovery fifteen years ago. Because of the outstanding photoluminescence properties, photostability, low toxicity, and low cost, CDs have potential to replace traditional semiconductor quantum dots which have serious drawbacks of toxicity and high cost. This review covers the common top-down and bottom-up methods for the synthesis of CDs, different categories of CD precursors (small molecules, natural polymers, and synthetic polymers), one-pot and multi-step methods to produce CDs/photocatalyst composites, and recent advances of CDs on photocatalysis applications mostly in pollutant degradation and energy areas. A broad range of precursors forming fluorescent CDs are discussed, including small molecule sole or dual precursors, natural polymers such as pure polysaccharides and proteins and crude bio-resources from plants or animals, and various synthetic polymer precursors with positive, negative, neutral and hydrophilic, hydrophobic, or zwitterionic feature. Because of the wide light absorbance, excellent photoluminescence properties and electron transfer ability, CDs have emerged as a new type of photocatalyst. Recent work of CDs as sole photocatalyst or in combination with other materials (e.g., metal, metal sulfide, metal oxide, bismuth-based semiconductor, or other traditional photocatalysts) to form composite catalyst for various photocatalytic applications are reviewed. Possible future directions are proposed at the end of the article on mechanistic studies, production of CDs with better controlled properties, expansion of polymer precursor pool, and systematic studies of CDs for photocatalysis applications.