Evidence for a trap-and-flip mechanism in a proton-dependent lipid transporter

Transport of lipids across membranes is fundamental for diverse biological pathways in cells. Multiple ion-coupled transporters participate in lipid translocation, but their mechanisms remain largely unknown. Major facilitator superfamily (MFS) lipid transporters play central roles in cell wall synthesis, brain development and function, lipids recycling, and cell signaling. Recent structures of MFS lipid transporters revealed overlapping architectural features pointing towards a common mechanism. Here we used cysteine disulfide trapping, molecular dynamics simulations, mutagenesis analysis, and transport assays in vitro and in vivo, to investigate the mechanism of LtaA, a proton-dependent MFS lipid transporter essential for lipoteichoic acids synthesis in the pathogen Staphylococcus aureus. We reveal that LtaA displays asymmetric lateral openings with distinct functional relevance and that cycling through outward- and inward-facing conformations is essential for transport activity. We demonstrate that while the entire amphipathic central cavity of LtaA contributes to lipid binding, its hydrophilic pocket dictates substrate specificity. We propose that LtaA catalyzes lipid translocation by a trap-and-flip mechanism that might be shared among MFS lipid transporters

Classifying Façade Colors in Residential Buildings Based on Color-Emotional Scales

The lack of facade color control programs in urban planning policies in Iran and the choice of facade color based on the designer’s taste make it necessary to design façade colors based on scientific principles and users’ evaluations. In color studies, emotional scales have been used to describe color. Due to the relative nature of emotional terms and the lack of consensus on definitions of these scales under the influence of contextual factors and individual characteristics of users, there is a need to redefine these scales in the context of Iran.This study aims to identify and determine the scales and components to classify the color combination of the façade. For this purpose, a combination of qualitative and quantitative methods was used. Twenty experts in the field of design and color participated in the Delphi survey, and the data were analyzed using the Q method. The finding presented three bipolar scales: temperature, harmony, and weight, to classify the facade color combination. In the next step, through semi-structured interviews with five architects and urban planners, components were determined to describe these three scales. Then, the authors of the study prepared a questionnaire to confirm the components completed by 20 former experts. Components affecting three scales and selected photos of each scale were extracted by analyzing data using the Q method in two steps. The quantitative values were collected through the color strip and HSL system codes of the final photos based on the percentage of color area in the façade, the number of hues, and their temperature, lightness, and saturation. Based on the results, the façade color combinations can be classified into eight treatments: cool-harmonious-light, cool-harmonious-heavy, cool-contrasting-light, cool-contrasting-heavy, warm-harmonious-light, warm-harmonious-heavy, warm-contrasting-light, and warm-contrasting-heavy, each of which can be defined using quantitative values

Sandwich structure polymer electrolyte membranes containing phosphotungstic acid immobilized electospun nanofibers

The advances in proton exchange membranes (PEM)s is critical for improving the performance of fuel cells [1]. Membranes compromising perfluorosulfonic acid polymers such as Nafion have been used extensively due to their desired conductivity and stability. However, these materials need to be saturated with water to obtain practical level of proton conductivity. There is a strong demand for the PEMs to work at lower relative humidity or under anhydrous conditions because the electrochemical reactions will be accelerated and water management of fuel cell will be simpler. Various designing strategies and advanced materials have been developed to mitigate for this issue without causing serious loss in proton conductivity or stability [2]. Among all, the introducing of inorganic proton conductors such as heteropoly acids have been considered widely. Generally, HPAs (such as phosphotungstic acid H3PW12O40, PWA) have a very strong Brønsted acidity approaching the superacid region (more acidic than Nafion) [3]. In this work, high level of PWA was self-anchored onto nylon electrospun nanofiberous sheet (Figure 1b). Sandwich structured proton conducting membranes were fabricate by assembling nanofibrous central layer with outer Nafion layers (Figure 1b). Since the PWA is attached to the polymer backbones, the risk of leaching out is minimized. Moreover, the significant synthetic versatility of the method helps to increase PWA immobilization level. As shown in the Figure 1c, proton conductivity of as high as 60 mS cm-1 at 30 °C was achieved which is comparable with Nafion 115. The durability of the proton conductivity of sandwiched membrane

A simple thermal treatment synthesis and characterization of Ni-Zn ferrite (Ni0.5Zn0.5Fe2O4) nanocrystals

Cubic structured nickel-zinc ferrite nanoparticles (Ni0.5Zn0.5Fe2O4) have been synthesized by thermal treatment method. This simple procedure employed an aqueous solution containing only metal nitrates as precursors, polyvinyl pyrrolidone as a capping agent, and deionized water as a solvent. The solution was thoroughly stirred for 2 hour, dried at 353 K for 3 hour, the dried material crushed into powder and calcined the powder at 873 K to remove organic substances and crystallize the particles. The microstructure properties of the prepared ferrite nanoparticles were measured using FTIR, XRD, TEM, and EDX and the magnetic properties were determined using VSM and EPR. The average particle size increased from 7 to 22 nm with the increase of calcination temperature from 723 to 873 K. The saturation magnetization, coercivity field, and g-factor increased respectively from 24 emu/g, 11 G, and 2.0673at 723 K to 38 emu/g, 60 G, and 2.1227 at 873 K. This method offers simplicity, a low cost, and an environmentally friendly operation since it produces no by-product effluents

Green Synthesized Magnesium Oxide Nanoparticles Reinforce Osteogenesis Properties of Bacterial Cellulose Scaffolds for Bone Tissue Engineering Applications: An In Vitro Assessment

Objective: The use of biocompatible scaffolds with appropriate characteristics to treat large bone defects has attractedsignificant attention. The main objective of the current study is to fabricate a 3D nanocomposite structure that containsgreen synthesized magnesium oxide nanoparticles (MgONPs) and bacterial cellulose (BC) nanofibres, as a bioscaffoldfor bone regeneration.Materials and Methods: In this experimental study, Camellia sinensis extract was used as the green method tosynthesize MgONPs. The synthesized hydrogels were evaluated for their porosity, morphology, degradation rate,mechanical features, cell attachment, and cytocompatibility. Osteogenic differentiation was assessed by alkalinephosphatase (ALP) activity, real-time reverse transcription-polymerase chain reaction (RT-PCR), and alizarin redstaining.Results: MgONPs significantly increased both mechanical strength (P=0.009) and porosity (P=0.01) of the BChydrogels. Human MG-63 osteoblast proliferation significantly increased in the MgONP-BC group compared to thepure BC group (P=0.003). Expression rates of both the ALP (P=0.001) and osteocalcin (OCN) genes were significantlyenhanced in cells seeded on the MgONP-incorporated BC. MG-63 cells had significantly greater calcium depositionand ALP activity (P=0.002) on the MgONP-BC scaffold compared to the BC at day 21.Conclusion: The MgONP-BC scaffold can promote the osteogenic activity of osteoblast-like cells, which indicates itstherapeutic potential for bone tissue regeneration

Toksikopatološke promjene izazvane kombiniranom izloženosti buci i toluenu u novozelandskih bijelih kunića

Noise and toluene can have significant adverse effects on different systems in the human body, but little is known about their combination. The aim of this study was to see how their combined action reflects on serum levels of inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), body weight, and pathological changes in the heart, lung, stomach, and spleen tissues. To do that we exposed New Zealand rabbits to 1000 mg/L toluene and 100 dB of white noise in a chamber specifically designed for the purpose over two consecutive weeks. Serum levels of TNF-α and IL-1β were measured with the enzyme-linked immunosorbent assay (ELISA), whereas Bax and Bcl-2 expressions in tissues were determined with real-time polymerase chain reaction (PCR). Noise and toluene changed TNF-α and IL-1β serum levels on different days following the end of exposure and significantly increased the Bax/Bcl-2 ratio in the lung and spleen. In addition, they induced different pathological changes in the heart, lung, spleen, and stomach tissues. This study has confirmed that exposure to noise and toluene can induce a range of toxicopathological changes, probably by inducing inflammatory pathways and apoptosis, but their combined effects look weaker than those of its components, although histopathological findings suggest the opposite.Buka i toluen mogu prouzročiti značajne štetne posljedice u različitim organskim sustavima u ljudi, ali je malo poznato kako djeluju zajedno. Stoga je cilj ovog istraživanja bio utvrditi kako izloženost njihovoj kombinaciji utječe na razine upalnih citokina u serumu [tumorskoga nekrotskog čimbenika alfa (TNF-α) i interleukina 1 beta (IL-1β)], na tjelesnu masu te na apoptotske i histopatološke promjene na srčanom, plućnom, želudčanom i slezenskom tkivu. U tu smo svrhu novozelandske kuniće izložili buci (100 dB) i/ili toluenu (1000 mg/L) u posebnoj komori u neprekidnom trajanju od dva tjedna. Razine TNF-α i IL-1β izmjerene su u 14 dana nakon svršetka izloženosti pomoću imunoenzimske metode ELISA, a ekspresije proteina Bax i Bcl-2 povezanih s apoptozom pomoću kvantitativne polimerazne lančane reakcije (engl. real-time polymerase chain reaction, PCR). Buka i toluen, zasebno i u kombinaciji, doveli su do različitih promjena razina TNF-α i IL-1β u serumu te značajno povećali omjer proteina Bax/Bcl-2 u plućima i slezeni. Usto su prouzročili različite patološke promjene u srčanom, plućnom, slezenskom i želučanom tkivu. Istraživanje je potvrdilo da izloženost buci i toluenu dovodi do cijelog niza toksikopatoloških promjena, vjerojatno tako što pokreće upalne putove i mehanizme apoptoze. Također se doima da kombinirana izloženost ima slabije djelovanje od djelovanja svake sastavnice zasebno, premda histopatološki nalazi upućuju na suprotno

Targeting the PI3K/Akt/mTOR Signaling Pathway: Applications of Nanotechnology

Mammalian target of rapamycin (mTOR), as an axial mediator of multiple cell growth pathways, is in connection with several other proteins that are involved in the regulation of homeostasis in the cell function. mTOR"s signaling pathway participates in and integrates a variety of environmental cues to control cancer cell and normal tissue development. mTOR and its inhibitors including the rapamycin analogues are attractive therapeutic indication to clinical trials for treating various types of cancers, with or without inhibitors of other signaling pathways. Despite the promising results in cancer treatment, low water solubility of rapamycin is shown to decrease its therapeutic efficacy. To reach an acceptable level of efficacy, high distribution and accepted dispersing of utilized drugs in control of mTOR signaling pathway, nanomaterials-based drug delivery can play an important role. Evaluation of the mechanisms and therapeutic effects of nanoparticle-based mTOR modulation can be useful in developing safe strategies in treatment of cancer. Regarding the clinical importance of mTOR deregulation in human diseases, hereby, we address the recent progress in the field of nanoparticle-based mTOR targeted therapy

Characterization and conduction mechanism of La5/8Sr3/8MnO3 thin films prepared by pulsed laser deposition on different substrates

The La5/8Sr3/8MnO3 (LSMO) thin films were directly grown on MgO and Si wafer substrates by Pulsed Laser Deposition (PLD) technique. The films were characterized using X-ray diffraction (XRD), field emission-scanning electron microscope (FE-SEM). The electrical and magnetic properties of films are studied. From the XRD patterns, the films are found polycrystalline single-phases. The highest magnetoresistance (MR) value obtained was −17.21% for LSMO/MgO film followed by −15.65% for LSMO/Si film at 80K in a 1T magnetic field. Transition temperature (TP) is 224K for LSMO/MgO and 200K for LSMO/Si film. The films exhibit a ferromagnetic transition at temperature (TC) around 363K for LSMO/MgO and 307K for LSMO/Si film. For LSMO/MgO, the high Curie temperature such as 363K is one of the high TC in all LSMO thin films and as our knowledge, is the highest value that is reported in literature for MgO substrates with high lattice mismatch parameter. The conduction mechanisms for both films have been extensively investigated. In the metallic regime, resistivity seems to emanate from the electron–electron (major) and electron-magnon (phonon) scattering processes. For both films in the range of T >TP, the resistivity data were well fitted by both variable range hopping (VRH) and small polaron hopping (SPH) models giving higher density state, and lower activation energy and Mott temperature T0 for LSMO/Si film than those for LSMO/MgO film. The high TC such as 363K makes these LSMO/MgO films very useful for room temperature magnetic devices

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks