| 1. |
- Lozano, Rafael, et al.
(författare)
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Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
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Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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| 2. |
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| 3. |
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| 4. |
- Jena, Manoj Kumar, et al.
(författare)
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Molecular complexity of mammary glands development : a review of lactogenic differentiation in epithelial cells
- 2023
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Ingår i: Artificial Cells, Nanomedicine and Biotechnology. - 2169-1401. ; 51:1, s. 491-508
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Tidskriftsartikel (refereegranskat)abstract
- The mammary gland is a dynamic organ with various physiological processes like cellular proliferation, differentiation, and apoptosis during the pregnancy-lactation-involution cycle. It is essential to understand the molecular changes during the lactogenic differentiation of mammary epithelial cells (MECs, the milk-synthesizing cells). The MECs are organized as luminal milk-secreting cells and basal myoepithelial cells (responsible for milk ejection by contraction) that form the alveoli. The branching morphogenesis and lactogenic differentiation of the MECs prepare the gland for lactation. This process is governed by many molecular mediators including hormones, growth factors, cytokines, miRNAs, regulatory proteins, etc. Interestingly, various signalling pathways guide lactation and understanding these molecular transitions from pregnancy to lactation will help researchers design further research. Manipulation of genes responsible for milk synthesis and secretion will promote augmentation of milk yield in dairy animals. Identifying protein signatures of lactation will help develop strategies for persistent lactation and shortening the dry period in farm animals. The present review article discusses in details the physiological and molecular changes occurring during lactogenic differentiation of MECs and the associated hormones, regulatory proteins, miRNAs, and signalling pathways. An in-depth knowledge of the molecular events will aid in developing engineered cellular models for studies related to mammary gland diseases of humans and animals.
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| 5. |
- Kim, Min Seo, et al.
(författare)
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Global burden of peripheral artery disease and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2023
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Ingår i: The Lancet Global Health. - : Elsevier. - 2214-109X. ; 11:10, s. E1553-E1565
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peripheral artery disease is a growing public health problem. We aimed to estimate the global disease burden of peripheral artery disease, its risk factors, and temporospatial trends to inform policy and public measures.Methods: Data on peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed.Findings: In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99 center dot 2-128 center dot 4), with a global prevalence of 1 center dot 52% (95% UI 1 center dot 33-1 center dot 72), of which 42 center dot 6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14 center dot 91% [12 center dot 41-17 center dot 87] in those aged 80-84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69 center dot 4% (64 center dot 2-74 center dot 3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles.Interpretation: The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors.
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| 6. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 7. |
- Kumar, Manoj, et al.
(författare)
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Arsenic distribution and mobilization : A case study of three districts of uttar pradesh and bihar (india)
- 2015
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Ingår i: Safe and Sustainable Use of Arsenic-Contaminated Aquifers in the Gangetic Plain. - Cham : Springer Publishing Company. - 9783319161242 - 9783319161235 ; , s. 111-123
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Tectonic evolution of Himalayas is related to high erosional potential and substantial sediment transport. Fluvial deposition of clastic material in the Middle Gangetic plain (MGP) is mainly governed by crustal deformation and climatic condition of Himalayas (Singh M, Singh IB, Müller G, Geomorphology 86:144-175, 2007). Seven large Asian rivers-Ganga, Indus, Brahmaputra, Yangtze, Huang He or Yellow River, Salween and Mekong-are fed by Himalayan glaciers which are supplying ~30 % of the global sediments to the ocean (Milliman JD, Meade RH, J Geol 9:1-19, 1983; Singh VB, Ramanathan AL, Pottakkal JG, Kumar M, J Asian Earth Sci 79:224-234, 2014, 2005). High flux of sediment transported from different terrain of Himalayas is product of geologically young rock formation (Singh VB, Ramanathan AL, Pottakkal JG, Kumar M, J Asian Earth Sci 79:224-234, 2014). It provides an opportunity to study the fluvial system and post-depositional changes in sediment water interaction depending on the degree of mobility of element under the altered environmental conditions. Arsenic (As) contamination of groundwater is a global problem. Understanding of As mobilization from sediments to As-contaminated aquifers is important for water quality management in areas of MGP of India.
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| 8. |
- Awasthi, Mukesh Kumar, et al.
(författare)
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Advanced approaches for resource recovery from wastewater and activated sludge: A review
- 2023
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Ingår i: Bioresource Technology. - 0960-8524 .- 1873-2976. ; 384
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Forskningsöversikt (refereegranskat)abstract
- Due to resource scarcity, current industrial systems are switching from waste treatment, such as wastewater treatment and biomass, to resource recovery (RR). Biofuels, manure, pesticides, organic acids, and other bioproducts with a great market value can be produced from wastewater and activated sludge (AS). This will not only help in the transition from a linear economy to a circular economy, but also contribute to sustainable development. However, the cost of recovering resources from wastewater and AS to produce value-added products is quite high as compared to conventional treatment methods. In addition, most antioxidant technologies remain at the laboratory scale that have not yet reached the level at industrial scale. In order to promote the innovation of resource recovery technology, the various methods of treating wastewater and AS to produce biofuels, nutrients and energy are reviewed, including biochemistry, thermochemistry and chemical stabilization. The limitations of wastewater and AS treatment methods are prospected from biochemical characteristics, economic and environmental factors. The biofuels derived from third generation feedstocks, such as wastewater are more sustainable. Microalgal biomass are being used to produce biodiesel, bioethanol, biohydrogen, biogas, biooils, bioplastics, biofertilizers, biochar and biopesticides. New technologies and policies can promote a circular economy based on biological materials.
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| 9. |
- Li, Yue, et al.
(författare)
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Sustainable Conversion of Biowaste to Energy to Tackle the Emerging Pollutants: A Review
- 2023
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Ingår i: Current Pollution Reports. - : Springer. - 2198-6592.
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Forskningsöversikt (refereegranskat)abstract
- Biowaste is a major source of organic material that can be converted into energy through various processes such as anaerobic digestion, composting, and pyrolysis. However, emerging pollutants, such as pharmaceuticals, pesticides, herbicides, and personal and household products, are a growing concern in wastewater treatment that can be effectively removed by biowaste-to-energy processes. While these contaminants pose significant challenges, the development and implementation of effective monitoring programs and risk assessment tools help to mitigate their impact on human health and the environment. Likewise, monitoring programs, challenges, legislations, and risk assessment tools are essential for understanding and managing the risks associated with emerging pollutants. Biowaste recycling is an important aspect of a biocircular economy perspective as it involves the conversion of organic waste into valuable resources that can be reused sustainably. The review discusses the modern approaches that offer several advantages, including reducing the waste disposal and generating renewable energy while addressing emerging wastewater treatment pollutants. To achieve the goal of a circular economy, modern biotechnological approaches including anaerobic digestion, composting, bioleaching, bioremediation, and microbial fuel cells offer a sustainable and effective way to convert waste into valuable products. These bioproducts alongside energy generation using waste-to-energy technologies can provide economic benefits through revenue generation, reduced waste disposal costs, and improved resource efficiency. To achieve a biocircular economy for biowaste valorization, several stakeholders, including waste collectors, waste management companies, policymakers, and consumers need to be involved. The sustainable conversion of biowaste to energy is an essential and instrumental technology in environmental sustainability.
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| 10. |
- Kumar R, Avinash, et al.
(författare)
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The hydraulic and thermal performances of rectangular and square microchannel with different hydraulic diameters cooled by graphene–platinum hybrid nanofluid
- 2022
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Ingår i: Proceedings of the Institution of Mechanical Engineers, Part C: Journal of Mechanical Engineering Science. - : SAGE Publications. - 2041-2983 .- 0954-4062. ; 236:13, s. 7473-7483
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this paper is to analyze the effect of hydraulic diameter and channel shape on the thermal and hydrodynamic characteristics of a microchannel cooled by Graphene–Platinum/water hybrid nanofluid for electronic cooling applications. The study was performed numerically using mathematical software called Maple 19.0. Microchannels having square and rectangular cross-sections, and hydraulic diameters ranging from 200 µm to 1,000 µm were taken into consideration. Thermal resistance, heat transfer coefficient, pressure drop, and friction factor were evaluated for different conditions and their corresponding graphs are presented and discussed. It was evident from the results that low thermal resistance and high heat transfer coefficient was achieved upon decreasing the hydraulic diameter, which is favorable for the cooling of electronic chips and devices. Based on the Reynolds number, the heat transfer coefficient increased by 2–4 times for both rectangular and square microchannels, on decreasing the hydraulic diameter from highest value (1,000 µm) to lowest value (200 µm). However, friction factor and pressure drop increased for channels with lower hydraulic diameters. In addition, rectangular microchannels exhibited better heat transfer performance, while square microchannels had lower friction factor and pressure drop. Rectangular microchannels presented a maximum enhancement of 30% in heat transfer coefficient and a reduction of 18% in thermal resistance, when compared to square microchannels. The results also suggested that the performance of microchannels with 500 µm hydraulic diameter is balanced, considering both heat transfer performance and pressure drop constraints.
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| 11. |
- Mohan, Gowtham, et al.
(författare)
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Experimental investigation of a novel solar thermal polygeneration plant in United Arab Emirates
- 2016
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Ingår i: Renewable energy. - : Elsevier BV. - 0960-1481 .- 1879-0682. ; 91, s. 361-373
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Tidskriftsartikel (refereegranskat)abstract
- The demands for space air conditioning and clean drinking water are relatively high in Middle East North African (MENA) countries. A sustainable and innovative approach to meet these demands along with the production of domestic hot water is experimentally investigated in this paper. A novel solar thermal poly-generation (STP) pilot plant is designed and developed for production of chilled water for air conditioning using absorption chiller, clean drinking water with membrane distillation units and domestic hot water by heat recovery. The STP system is developed with a flexibility to operate in four different modes: (i) solar cooling mode (ii) cogeneration of drinking water and domestic hot water (iii) cogeneration of cooling and desalination (iv) trigeneration. Operational flexibility allows consumers to utilize the available energy based on seasonal requirements. Performance of STP system is analyzed during summer months in RAKRIC research facility. Energy flows in STP pilot plant during peak load operations are analyzed for all four modes. STP system with trigeneration mode utilizes 23% more useful energy compared to solar cooling mode, which improves overall efficiency of the plant. Economic benefits of STP with trigeneration mode are evaluated with fuel cost inflation rate of 10%. STP plant has potential payback period of 9.08 years and net cumulative savings of $454,000 based on economic evaluation.
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| 12. |
- Pandey, Kavita, et al.
(författare)
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Improving electron transport in the hybrid perovskite solar cells using CaMnO3-based buffer layer
- 2018
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Ingår i: Nano Energy. - : ELSEVIER SCIENCE BV. - 2211-2855 .- 2211-3282. ; 45, s. 287-297
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Tidskriftsartikel (refereegranskat)abstract
- In the present article, the detailed analyses of interface properties and device performance of inorganic perovskite CaMnO3-based buffer layer hybrid perovskite solar cell have been undertaken. Analyses are based on ab initio simulations and macroscopic modelling. A thorough study of electronic and optical properties and interface charge dynamics revealed that CaMnO3 presents a better candidate for the electron transport material in thin film hole transporting material free hybrid perovskite solar cells with the planar architecture than the most common anatase TiO2. This result is founded on the more appropriate band gap and better band alignment with the hybrid perovskite, leading to the faster charge carrier mobility, improved charge transfer and reduced exciton recombination. The results from theoretical simulations are justified by the solar cell model, which explored the basic cell characteristics and parameters: open circuit voltage, short circuit current, fill factor and efficiency, as the functions of cell performance factors, like defect density, diffusion length, absorber layer thickness and band offset. Our model suggests an unoptimized device with a photo-conversion efficiency of almost 10% for the low defect concentrations under 10(15). With efficiency in the upper range for HTM free perovskite solar cells, we propose that the CaMnO3-based solar cell poses as an improvement upon the up to now most frequently used ones and provides important step toward their commercialisation.
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| 13. |
- Sundell, David, et al.
(författare)
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AspWood : High-Spatial-Resolution Transcriptome Profiles Reveal Uncharacterized Modularity of Wood Formation in Populus tremula
- 2017
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Ingår i: The Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 29:7, s. 1585-1604
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Tidskriftsartikel (refereegranskat)abstract
- Trees represent the largest terrestrial carbon sink and a renewable source of ligno-cellulose. There is significant scope for yield and quality improvement in these largely undomesticated species, and efforts to engineer elite varieties will benefit from improved understanding of the transcriptional network underlying cambial growth and wood formation. We generated high-spatial-resolution RNA sequencing data spanning the secondary phloem, vascular cambium, and wood-forming tissues of Populus tremula. The transcriptome comprised 28,294 expressed, annotated genes, 78 novel protein-coding genes, and 567 putative long intergenic noncoding RNAs. Most paralogs originating from the Salicaceae whole-genome duplication had diverged expression, with the exception of those highly expressed during secondary cell wall deposition. Coexpression network analyses revealed that regulation of the transcriptome underlying cambial growth and wood formation comprises numerous modules forming a continuum of active processes across the tissues. A comparative analysis revealed that a majority of these modules are conserved in Picea abies. The high spatial resolution of our data enabled identification of novel roles for characterized genes involved in xylan and cellulose biosynthesis, regulators of xylem vessel and fiber differentiation and lignification. An associated web resource (AspWood, http://aspwood.popgenie.org) provides interactive tools for exploring the expression profiles and coexpression network.
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| 14. |
- Sundell, David, et al.
(författare)
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High-spatial-resolution transcriptome profiling reveals uncharacterized regulatory complexity underlying cambial growth and wood formation in Populus tremula
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Trees represent the largest terrestrial carbon sink and a renewable source of ligno-cellulose. There is significant scope for yield and quality improvement in these largely undomesticated species, however, efforts to engineer new, elite varieties are constrained by the lack of a comprehensive understanding of the transcriptional network underlying cambial growth and wood formation. We generated RNA Sequencing transcriptome data for four mature, wild-growing aspens (Populus tremula) from high-spatial-resolution tangential cryosection series spanning the secondary phloem, vascular cambium, expanding and secondary cell wall forming xylem cells, cell death zone and the previous years annual ring. The transcriptome comprised 28,294 expressed, previously annotated protein-coding genes, 78 novel protein-coding genes and 567 long intergenic non-coding RNAs. Most paralogs originating from the Salicaceae whole genome duplication had diverged expression, with the notable exception of those with high expression during secondary cell wall deposition. We performed co-expression network analysis to identify central transcriptional modules and associated several of these with known biological processes. This revealed previously uncharacterized complexity underlying the regulation of cambial growth and wood formation, with modules forming a continuum of activated processes across the tissues. The high spatial resolution suggested novel roles for known genes involved in xylan and cellulose biosynthesis, regulators of xylem vessel and fiber differentiation and components of lignification. The associated web resource (AspWood, http://aspwood.popgenie.org) integrates the data within a set of interactive tools for exploring the co-expression network of cambial growth and wood formation.
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| 15. |
- Bandaru, Manoj Kumar, 1987-, et al.
(författare)
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Apoc2 mutant zebrafish: a model for hypertriglyceridemia and early-stage atherosclerosis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Zebrafish larvae in a hypertriglyceridemic background can be useful to identify and characterize causal genes for triglyceride metabolism. A previous, small-scale study suggested that apolipoprotein C-II (apoc2)-mutant zebrafish larvae can be used to model hypertriglyceridemia-induced atherosclerosis. We aimed to replicate these findings in a large-scale study and asses if APOC-II may represent a useful therapeutic target. We generated apoc2 mutant zebrafish using CRISPR-Cas9 and examined cardiometabolomic traits in their offspring (F1 generation). Systematic characterization of 384 larvae using our image and assay-based, high-throughput pipeline showed that compound heterozygous larvae for loss of function mutations in apoc2 (n=35) have higher whole-body levels of triglycerides (0.71±0.16 SD), HDL cholesterol (0.32±0.15 SD) and total cholesterol (0.37±0.18 SD), and a trend for lower whole-body glucose levels (0.23±0.14 SD) compared with larvae without mutations in apoc2 (n=174). Such larvae also tended to have more vascular lipid deposition, however this effect did not reach significance (P=0.12). Interestingly, the trends for lower whole-body glucose levels and more vascular lipid deposition in larvae with anticipated loss of functional apoc2 reached significance when larvae (n=3812) from other screens, in which apoc2 was not experimentally perturbed were included as additional wildtype controls. Thus, our large-scale study confirms the role of apoc2 in hypertriglyceridemia and early-stage atherosclerosis. While apoc2 mutant zebrafish model can be used as a genetic background to identify and characterize causal genes for triglyceride metabolism, independent and opposite effects on triglycerides and glucose suggest that APOC-II is likely not a suitable target for prevention and treatment of coronary artery disease.
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| 16. |
- Bandaru, Manoj Kumar, 1987-, et al.
(författare)
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Image-based, in vivo characterization of cardiometabolic consequences of mutations in pcsk9
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Based on the association of loss-of-function mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) with low plasma LDL cholesterol levels, inhibition of the PCSK9 protein using monoclonal antibodies have emerged as an effective treatment option to lower LDL cholesterol levels and reduce the risk of coronary artery disease. Despite these beneficial effects, PCSK9 inhibitors may increase the risk of diabetes. In this study, we mimicked the mechanistic action of PCSK9 inhibitors in humans by inducing mutations in pcsk9 in zebrafish and examining their effects on dyslipidemia, early-stage atherosclerosis and diabetes-related traits in data from nearly 5000 zebrafish larvae. At 10 days of age, larvae with mutations in pcsk9 were characterized by lower whole-body LDL cholesterol levels (beta±SE -0.056±0.025 SD units) and protection against early-stage atherosclerosis, with less vascular lipid deposition (-0.133±0.035 SD) and less co-localization of macrophages with lipids (-0.086±0.032 SD). Mutant larvae also had fewer pancreatic β-cells (-0.153±0.055 SD). Thus, our findings in pcsk9 mutant larvae are in line with results from people carrying loss-of-function PCSK9 mutations, and are also in line with the effects of PCSK9 inhibitors in humans. Further, our results suggest that mutations in pcsk9 may increase the risk of diabetes through a direct effect on pancreatic β-cells.
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| 17. |
- Bandaru, Manoj Kumar, et al.
(författare)
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Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hundreds of loci have been robustly associated with circulating lipids, atherosclerosis and coronary artery disease; but for most loci the causal genes and mechanisms remain uncharacterized.Methods: We developed a semi-automated experimental pipeline for systematic, quantitative, large-scale characterization of mechanisms, drugs and genes associated with dyslipidemia and atherosclerosis in a zebrafish model system. We validated our pipeline using a dietary (n>2000), drug treatment (n>1000), and genetic intervention (n=384).Results: Our results show that five days of overfeeding and cholesterol supplementation had independent pro-atherogenic effects, which could be diminished by concomitant treatment with atorvastatin and ezetimibe. CRISPR-Cas9-induced mutations in orthologues of proof-of-concept genes resulted in higher LDL cholesterol levels (apoea), and more early stage atherosclerosis (apobb.1).Conclusions: In summary, our pipeline facilitates systematic, in vivo characterization of drugs and candidate genes to increase our understanding of disease etiology, and can likely help identify novel targets for therapeutic intervention.
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| 18. |
- Bandaru, Manoj Kumar, 1987-
(författare)
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Zebrafish models for large-scale genetic screens in dyslipidemia and atherosclerosis : Validation and application
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hundreds of loci have been robustly associated with circulating lipids, atherosclerosis and coronary artery disease; but for most loci the causal genes and mechanisms remain uncharacterized. The overall aim of my thesis is to develop and validate novel in vivo model systems that are suitable for high-throughput, image-based genetic screens in coronary artery disease and related traits, and use these model systems to systematically characterize positional candidate genes.In Study I, I developed an experimental pipeline to validate the suitability of zebrafish larvae as a model system for systematic, large-scale characterization of drugs and genes associated with dyslipidemia and atherosclerosis. Using this pipeline, I showed that five days of overfeeding and cholesterol supplementation have independent pro-atherogenic effects in zebrafish larvae, which could be diminished by concomitant treatment with atorvastatin and ezetimibe. CRISPR-Cas9-induced mutations in orthologues of proof-of-concept genes resulted in higher LDL cholesterol levels (apoea), and more early stage atherosclerosis (apobb.1). Finally, the pipeline helped me to identify putative causal genes for circulating lipids and early-stage atherosclerosis (LPAR2 and GATAD2A).In Study II, I characterized cardiometabolic traits in apoc2 mutant zebrafish larvae and found that, similar to humans, larvae with two non-functional apoc2 alleles have higher whole-body levels of triglycerides and total cholesterol, and more vascular lipid deposition than larvae without mutations in apoc2. Interestingly, apoc2 mutant larvae also had lower glucose levels after adjusting for triglyceride levels, suggesting that therapeutic stimulation of apoc2 to prevent hypertriglyceridemia may result in hyperglycemia. Still, zebrafish larvae with mutations in apoc2 can be a useful model to identify and characterize additional causal genes for triglyceride metabolism.In Study III, I examined the effects of mutations in pcsk9 on atherosclerosis and diabetes-related traits in nearly 5,000 zebrafish larvae. Similar to the loss-of-function mutations in PCSK9 in humans, larvae with mutations in pcsk9 had lower LDLc levels and were protected from early-stage atherosclerosis. Interestingly, mutations in pcsk9 also resulted in fewer pancreatic β-cells in 10 days old larvae, which suggests the higher risk of diabetes in humans with mutations in PCSK9 may result from a direct effect on the beta cell.Based on these large-scale proof-of-concept studies, my thesis confirms that zebrafish larvae can be used for large-scale, systematic genetic screens in dyslipidemia and early-stage atherosclerosis.
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| 19. |
- Basu, Bikramjit, et al.
(författare)
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Friction and Wear of Ceramics : Principles and Case Studies
- 2020
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- This book covers the area of tribology broadly, providing important introductory chapters to fundamentals, processing, and applications of tribology. The book is designed primarily for easy and cohesive understanding for students and practicing scientists pursuing the area of tribology with focus on materials. This book helps students and practicing scientists alike understand that a comprehensive knowledge about the friction and wear properties of advanced materials is essential to further design and development of new materials.The description of the wear micromechanisms of various materials will provide a strong background to the readers as how to design and develop new tribological materials. This book also places importance on the development of new ceramic composites in the context of tribological applications. The various sections of the book discuss fundamentals of nature and properties of materials, friction and wear of structural ceramics, bioceramics, biocomposites, and nanoceramics, as well as lightweight composites and friction and wear of ceramics in a cryogenic environment.Some of the key features of the book include: Fundamentals section highlights the salient issues of ceramic processing and mechanical properties of important oxide and non-oxide ceramic systems; State of the art research findings on important ceramic composites are included and an understanding on the behavior of silicon carbide (SiC) based ceramic composites in dry sliding wear conditions is presented as a case study; Erosion wear behavior of ceramics, in which case studies on high temperature erosion behavior of SiC based composites and zirconium diboride (ZrB2) based composites is also covered; Wear behavior of ceramic coatings is rarely discussed in any tribology related books therefore a case study explaining the abrasion wear behavior of WC-Co coating is provided. Finally an appendix chapter is included in which a collection of several types of questions including multiple choice, short answer and long answer ae provided.
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| 20. |
- Bjurhager, Ingela, et al.
(författare)
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Ultrastructure and Mechanical Properties of Populus Wood with Reduced Lignin Content Caused by Transgenic Down-Regulation of Cinnamate 4-Hydroxylase
- 2010
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 11:9, s. 2359-2365
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Tidskriftsartikel (refereegranskat)abstract
- Several key enzymes in lignin biosynthesis of Populus have been down-regulated by transgenie approaches to investigate their role in wood lignification and to explore their potential for lignin modification. Cinnamate 4-hydroxylase is an enzyme in the early phenylpropanoid pathway that has not yet been functionally analyzed in Populus. This study shows that down-regulation of cinnamate 4-hydroxylase reduced Klason lignin content by 30% with no significant change in syringyl to guaiacyl ratio. The lignin reduction resulted in ultrastructural differences of the wood and a 10% decrease in wood density. Mechanical properties investigated by tensile tests and dynamic mechanical analysis showed a decrease in stiffness, which could be explained by the lower density. The study demonstrates that a large modification in lignin content only has minor influences on tensile properties of wood in its axial direction and highlights the usefulness of wood modified beyond its natural variation by transgene technology in exploring the impact of wood biopolymer composition and ultrastructure on its material properties.
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| 21. |
- Clark, David, et al.
(författare)
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Management and outcomes following emergency surgery for traumatic brain injury – A multi-centre, international, prospective cohort study (the Global Neurotrauma Outcomes Study)
- 2020
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Ingår i: International Journal of Surgery Protocols. - : IJS Press. - 2468-3574. ; 20, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Traumatic brain injury (TBI) accounts for a significant amount of death and disability worldwide and the majority of this burden affects individuals in low-and-middle income countries. Despite this, considerable geographical differences have been reported in the care of TBI patients. On this background, we aim to provide a comprehensive international picture of the epidemiological characteristics, management and outcomes of patients undergoing emergency surgery for traumatic brain injury (TBI) worldwide. Methods and analysis: The Global Neurotrauma Outcomes Study (GNOS) is a multi-centre, international, prospective observational cohort study. Any unit performing emergency surgery for TBI worldwide will be eligible to participate. All TBI patients who receive emergency surgery in any given consecutive 30-day period beginning between 1st of November 2018 and 31st of December 2019 in a given participating unit will be included. Data will be collected via a secure online platform in anonymised form. The primary outcome measures for the study will be 14-day mortality (or survival to hospital discharge, whichever comes first). Final day of data collection for the primary outcome measure is February 13th. Secondary outcome measures include return to theatre and surgical site infection. Ethics and dissemination: This project will not affect clinical practice and has been classified as clinical audit following research ethics review. Access to source data will be made available to collaborators through national or international anonymised datasets on request and after review of the scientific validity of the proposed analysis by the central study team.
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| 22. |
- Dixit, Rishibha, et al.
(författare)
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Effect of Various Growth Medium on the Physiology and De Novo Lipogenesis of a Freshwater Microalga Scenedesmus rotundus-MG910488 under Autotrophic Condition
- 2022
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Ingår i: Clean Technologies. - : MDPI. - 2571-8797. ; 4:3, s. 733-751
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Tidskriftsartikel (refereegranskat)abstract
- The microalga Scenedesmus rotundus, isolated from Jabalpur, Madhya Pradesh, India was designated as Scenedesmus rotundus-MG910488 after morphological and molecular identification. In this study, the effects of various autotrophic growth media on the physiology and lipid accumulation of this microalga were investigated. The cell density, amount of photosynthetic pigments, the productivity of biomass and lipid content and the cell morphology of the microalga were shown to be significantly affected by the variation in growth media. The highest biomass of 754.56 +/- 14.80 mg L-1 with biomass productivity of 37.73 +/- 0.74 mg L(-1)day(-1) was achieved when this microalgae was cultivated in the Zarrouk's medium, whereas the highest lipid content of 33.30 +/- 1.21% was observed in the BG-11 medium. The results confirm that the BG-11 is a cost-effective and efficient growth medium for this microalga. It also shows that the ingredients of the growth medium and its concentration influence the growth and synthesis of biomolecules produced by microalga. The biodiesel produced from obtained lipids was qualitatively estimated by Gas Chromatography-Mass Spectroscopy (GC-MS), Nuclear Magnetic Resonance (H-1, C-13 NMR) and Fourier Transform-Infrared Spectroscopy (FT-IR), which indicate the presence of oleic acid methyl ester, linoleic acid methyl ester and palmitic acid methyl ester as the leading fatty acid methyl esters (FAME) in the samples, which make this strain an ideal feedstock for biodiesel production.
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| 23. |
- Gallardo, Rodrigo, et al.
(författare)
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De novo design of a biologically active amyloid
- 2016
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 354:6313, s. 720-
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Tidskriftsartikel (refereegranskat)abstract
- Most human proteins possess amyloidogenic segments, but only about 30 are associated with amyloid-associated pathologies, and it remains unclear what determines amyloid toxicity. We designed vascin, a synthetic amyloid peptide, based on an amyloidogenic fragment of vascular endothelial growth factor receptor 2 (VEGFR2), a protein that is not associated to amyloidosis. Vascin recapitulates key biophysical and biochemical characteristics of natural amyloids, penetrates cells, and seeds the aggregation of VEGFR2 through direct interaction. We found that amyloid toxicity is observed only in cells that both express VEGFR2 and are dependent on VEGFR2 activity for survival. Thus, amyloid toxicity here appears to be both protein-specific and conditional-determined by VEGFR2 loss of function in a biological context in which target protein function is essential.
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| 24. |
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| 25. |
- Garbom, Sara, et al.
(författare)
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Phenotypic characterization of a virulence-associated protein, VagH, of Yersinia pseudotuberculosis reveals a tight link between VagH and the type III secretion system.
- 2007
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Ingår i: Microbiology. - : Society for General Microbiology. - 1350-0872 .- 1465-2080. ; 153:Pt 5, s. 1464-73
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a number of attenuated mutants of Yersinia pseudotuberculosis have been identified using a bioinformatics approach. One of the target genes identified in that study was vagH, which the authors now characterized further. VagH shows homology to HemK of Escherichia coli, possessing methyltransferase activity similar to that of HemK, and targeting release factors 1 and 2. Microarray studies comparing the wild-type and the vagH mutant revealed that the mRNA levels of only a few genes were altered in the mutant. By proteome analysis, expression of the virulence determinant YopD was found to be increased, indicating a possible connection between VagH and the virulence plasmid-encoded type III secretion system (T3SS). Further analysis showed that Yop expression and secretion were repressed in a vagH mutant. This phenotype could be suppressed by trans-complementation with the wild-type vagH gene or by deletion of the negative regulator yopD. Also, in a similar manner to a T3SS-negative mutant, the avirulent vagH mutant was rapidly cleared from Peyer's patches and could not reach the spleen after oral infection of mice. In a manner analogous to that of T3SS mutants, the vagH mutant could not block phagocytosis by macrophages. However, a vagH mutant showed no defects in the T3SS-independent ability to proliferate intracellularly and replicated to levels similar to those of the wild-type in macrophages. In conclusion, the vagH mutant exhibits a virulence phenotype similar to that of a T3SS-negative mutant, indicating a tight link between VagH and type III secretion in Y. pseudotuberculosis.
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