Assembly of the peripheral stalk of ATP synthase in human mitochondria.

The adenosine triphosphate (ATP) synthase in human mitochondria is a membrane bound assembly of 29 proteins of 18 kinds organized into F1-catalytic, peripheral stalk (PS), and c8-rotor ring modules. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, imported into the mitochondrial matrix, and assembled into the complex with the mitochondrial gene products ATP6 and ATP8. Intermediate vestigial ATPase complexes formed by disruption of nuclear genes for individual subunits provide a description of how the various domains are introduced into the enzyme. From this approach, it is evident that three alternative pathways operate to introduce the PS module (including associated membrane subunits e, f, and g). In one pathway, the PS is built up by addition to the core subunit b of membrane subunits e and g together, followed by membrane subunit f. Then this b-e-g-f complex is bound to the preformed F1-c8 module by subunits OSCP and F6 The final component of the PS, subunit d, is added subsequently to form a key intermediate that accepts the two mitochondrially encoded subunits. In another route to this key intermediate, first e and g together and then f are added to a preformed F1-c8-OSCP-F6-b-d complex. A third route involves the addition of the c8-ring module to the complete F1-PS complex. The key intermediate then accepts the two mitochondrially encoded subunits, stabilized by the addition of subunit j, leading to an ATP synthase complex that is coupled to the proton motive force and capable of making ATP

High-yield TiO(2) nanowire synthesis and single nanowire field-effect transistor fabrication

We report a facile method for synthesizing single-crystal rutile TiO 2 nanowires using atmospheric-pressure, chemical vapor deposition with Ti and TiO as precursors. The synthesis is found to depend critically on the predeposition of a layer of metallic Ti on the Ni catalysts layer. The omission of this step seems previously to have impeded the efficient synthesis of titania nanowires. Single-nanowire field-effect transistors showed the TiO2 nanowires to be n -type semiconductors with conductance activation energy of ???58 meV.open242

Flash flood susceptibility assessment and zonation by integrating analytic hierarchy process and frequency ratio model with diverse spatial data

Flash floods are the most dangerous kinds of floods because they combine the destructive power of a flood with incredible speed. They occur when heavy rainfall exceeds the ability of the ground to absorb it. The main aim of this study is to generate flash flood maps using Analytical Hierarchy Process (AHP) and Frequency Ratio (FR) models in the river’s floodplain between the Jhelum River and Chenab rivers. A total of eight flash flood-causative physical parameters are considered for this study. Six parameters are based on remote sensing images of the Advanced Land Observation Satellite (ALOS), Digital Elevation Model (DEM), and Sentinel-2 Satellite, which include slope, elevation, distance from the stream, drainage density, flow accumulation, and land use/land cover (LULC), respectively. The other two parameters are soil and geology, which consist of different rock and soil formations, respectively. In the case of AHP, each of the criteria is allotted an estimated weight according to its significant importance in the occurrence of flash floods. In the end, all the parameters were integrated using weighted overlay analysis in which the influence value of drainage density was given the highest weight. The analysis shows that a distance of 2500 m from the river has values of FR ranging from 0.54, 0.56, 1.21, 1.26, and 0.48, respectively. The output zones were categorized into very low, low, moderate, high, and very high risk, covering 7354, 5147, 3665, 2592, and 1343 km2, respectively. Finally, the results show that the very high flood areas cover 1343 km2, or 6.68% of the total area. The Mangla, Marala, and Trimmu valleys were identified as high-risk zones of the study area, which have been damaged drastically many times by flash floods. It provides policy guidelines for risk managers, emergency and disaster response services, urban and infrastructure planners, hydrologists, and climate scientists

Organization of Subunits in the Membrane Domain of the Bovine F-ATPase Revealed by Covalent Cross-linking.

The F-ATPase in bovine mitochondria is a membrane-bound complex of about 30 subunits of 18 different kinds. Currently, ∼85% of its structure is known. The enzyme has a membrane extrinsic catalytic domain, and a membrane intrinsic domain where the turning of the enzyme's rotor is generated from the transmembrane proton-motive force. The domains are linked by central and peripheral stalks. The central stalk and a hydrophobic ring of c-subunits in the membrane domain constitute the enzyme's rotor. The external surface of the catalytic domain and membrane subunit a are linked by the peripheral stalk, holding them static relative to the rotor. The membrane domain contains six additional subunits named ATP8, e, f, g, DAPIT (diabetes-associated protein in insulin-sensitive tissues), and 6.8PL (6.8-kDa proteolipid), each with a single predicted transmembrane α-helix, but their orientation and topography are unknown. Mutations in ATP8 uncouple the enzyme and interfere with its assembly, but its roles and the roles of the other five subunits are largely unknown. We have reacted accessible amino groups in the enzyme with bifunctional cross-linking agents and identified the linked residues. Cross-links involving the supernumerary subunits, where the structures are not known, show that the C terminus of ATP8 extends ∼70 Å from the membrane into the peripheral stalk and that the N termini of the other supernumerary subunits are on the same side of the membrane, probably in the mitochondrial matrix. These experiments contribute significantly toward building up a complete structural picture of the F-ATPase.This work was supported by the intramural program of the Medical Research Council (MRC Grant U105663150 (to J. E. W.)

Purification, characterization and crystallization of the F-ATPase from Paracoccus denitrificans.

The structures of F-ATPases have been determined predominantly with mitochondrial enzymes, but hitherto no F-ATPase has been crystallized intact. A high-resolution model of the bovine enzyme built up from separate sub-structures determined by X-ray crystallography contains about 85% of the entire complex, but it lacks a crucial region that provides a transmembrane proton pathway involved in the generation of the rotary mechanism that drives the synthesis of ATP. Here the isolation, characterization and crystallization of an integral F-ATPase complex from the α-proteobacterium Paracoccus denitrificans are described. Unlike many eubacterial F-ATPases, which can both synthesize and hydrolyse ATP, the P. denitrificans enzyme can only carry out the synthetic reaction. The mechanism of inhibition of its ATP hydrolytic activity involves a ζ inhibitor protein, which binds to the catalytic F₁-domain of the enzyme. The complex that has been crystallized, and the crystals themselves, contain the nine core proteins of the complete F-ATPase complex plus the ζ inhibitor protein. The formation of crystals depends upon the presence of bound bacterial cardiolipin and phospholipid molecules; when they were removed, the complex failed to crystallize. The experiments open the way to an atomic structure of an F-ATPase complex.his work was funded by the intramural programme of the Medical Research Council via MRC programme U105663150 to J.E.W., and by support from the Biotechnology and Biological Sciences Research Council to M.J.O.W

Monitoring the dynamic changes in vegetation cover using spatio-temporal remote sensing data from 1984 to 2020

Anthropogenic activities and natural climate changes are the central driving forces of global ecosystems and agriculture changes. Climate changes, such as rainfall and temperature changes, have had the greatest impact on different types of plant production around the world. In the present study, we investigated the spatiotemporal variation of major crops (cotton, rice, wheat, and sugarcane) in the District Vehari, Pakistan, from 1984 to 2020 using remote sensing (RS) technology. The crop identification was pre-processed in ArcGIS software based on Landsat images. After pre-processing, supervised classification was used, which explains the maximum likelihood classification (MLC) to identify the vegetation changes. Our results showed that in the study area cultivated areas under wheat and cotton decreased by almost 5.4% and 9.1% from 1984 to 2020, respectively. Vegetated areas have maximum values of NDVI (>0.4), and built-up areas showed fewer NDVI values (0 to 0.2) in the District Vehari. During the Rabi season, the temperature was increased from 19.93 °C to 21.17 °C. The average temperature was calculated at 34.28 °C to 35.54 °C during the Kharif season in the District Vehari. Our results showed that temperature negatively affects sugarcane, rice, and cotton crops during the Rabi season, and precipitation positively affects sugarcane, rice, and cotton crops during the Kharif season in the study area. Accurate and timely assessment of crop estimation and relation to climate change can give very useful information for decision-makers, governments, and planners in formulating policies regarding crop management and improving agriculture yields

METTL15 introduces N4-methylcytidine into human mitochondrial 12S rRNA and is required for mitoribosome biogenesis.

Post-transcriptional RNA modifications, the epitranscriptome, play important roles in modulating the functions of RNA species. Modifications of rRNA are key for ribosome production and function. Identification and characterization of enzymes involved in epitranscriptome shaping is instrumental for the elucidation of the functional roles of specific RNA modifications. Ten modified sites have been thus far identified in the mammalian mitochondrial rRNA. Enzymes responsible for two of these modifications have not been characterized. Here, we identify METTL15, show that it is the main N4-methylcytidine (m4C) methyltransferase in human cells and demonstrate that it is responsible for the methylation of position C839 in mitochondrial 12S rRNA. We show that the lack of METTL15 results in a reduction of the mitochondrial de novo protein synthesis and decreased steady-state levels of protein components of the oxidative phosphorylation system. Without functional METTL15, the assembly of the mitochondrial ribosome is decreased, with the late assembly components being unable to be incorporated efficiently into the small subunit. We speculate that m4C839 is involved in the stabilization of 12S rRNA folding, therefore facilitating the assembly of the mitochondrial small ribosomal subunits. Taken together our data show that METTL15 is a novel protein necessary for efficient translation in human mitochondria.Medical Research Council, UK [MC_UU_00015/4]; EMBO [ALFT 701-2013 to L.V.H]; ‘Fundação para a Ciência e a Tecnologia’ [PD/BD/105750/2014 to P.R.-G.]

Gold nanoprisms as a hybrid in vivo cancer theranostic platform for in situ photoacoustic imaging, angiography, and localized hyperthermia

The development of high-resolution nanosized photoacoustic contrast agents is an exciting yet challenging technological advance. Herein, antibody (breast cancer-associated antigen 1 (Brcaa1) monoclonal antibody)- and peptide (RGD)-functionalized gold nanoprisms (AuNprs) were used as a combinatorial methodology for in situ photoacoustic imaging, angiography, and localized hyperthermia using orthotopic and subcutaneous murine gastric carcinoma models. RGD-conjugated PEGylated AuNprs are available for tumor angiography, and Brcaa1 monoclonal antibody-conjugated PEGylated AuNprs are used for targeting and for in situ imaging of gastric carcinoma in orthotopic tumor models. In situ photoacoustic imaging allowed for anatomical and functional imaging at the tumor site. In vivo tumor angiography imaging showed enhancement of the photoacoustic signal in a time-dependent manner. Furthermore, photoacoustic imaging demonstrated that tumor vessels were clearly damaged after localized hyperthermia. This is the first proof-of-concept using two AuNprs probes as highly sensitive contrasts and therapeutic agents for in situ tumor detection and inhibition. These smart antibody/peptide AuNprs can be used as an efficient nanotheranostic platform for in vivo tumor detection with high sensitivity, as well as for tumor targeting therapy, which, with a single-dose injection, results in tumor size reduction and increases mice survival after localized hyperthermia treatment.National Basic Research Program of China (No. 2015CB931802)National Natural Science Foundation (China) (Nos. 81225010, 81327002, 31170961, 20771075, and 20803040)National High-Tech R&D Plan of China (No. 2014AA020700)Shanghai Science and Technology Fund (Nos. 13NM1401500 and 15DZ2252000

Risk factors for posttraumatic stress reactions among chinese students following exposure to a snowstorm disaster

<p>Abstract</p> <p>Background</p> <p>It is important to understand which factors increase the risk of posttraumatic stress disorder (PTSD) in adolescents. Previous studies have shown that the most important risk factors for PTSD include the type, severity, and duration of exposure to the traumatic events.</p> <p>Methods</p> <p>A cross-sectional survey was used to investigate the psychological symptoms associated with the aftermath of a snowstorm disaster in the Hunan province of China in January 2008. Students living in Hunan were surveyed at a three<b>-</b>month follow-up after the disaster. The questionnaire battery included the Impact of Event Scale-Revised (IES-R, trauma and symptoms associated with PTSD), the Chinese version of the Life Orientation Test-Revised (LOT-R, optimism and pessimism), the Chinese version of the Eysenck Personality Questionnaire (EPQ, neuroticism and extraversion), the Chinese Trait Coping Style Questionnaire (TCSQ, positive and negative coping styles), and a range of questions addressing social demographic characteristics and factors relating to the snowstorm. The survey was administered in school, and 968 students completed and returned the questionnaires.</p> <p>Results</p> <p>The results showed that 14.5% of the students had a total IES-R score ≥20. Students with greater school-to-home distances showed higher levels of posttraumatic stress symptoms than students who lived shorter distances from school. Students with emotional support from their teachers reported higher levels of posttraumatic stress symptoms (21.20%) than students without a teacher's emotional support (11.07%). The IES-R total and subscale scores correlated with all variables except extraversion. The binary logistic regression analysis results showed that the teacher's emotional support [odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.13-2.62], school-to-home distance (OR = 1.01, 95% CI = 1.00-1.01), negative coping (OR = 1.05; 95% CI = 1.02-1.08), and neuroticism (OR = 1.04, 95% CI = 1.02-1.06) were risk factors that predicted PTSD frequency and severity (percentage correct = 85.5%).</p> <p>Conclusions</p> <p>The risk factors that significantly impacted the onset of posttraumatic stress reactions in students living in Hunan, China following a snowstorm disaster were the school-to-home distance, negative coping, neuroticism, and teacher's emotional support.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London