| 1. |
- Ahmad, Shabbir, et al.
(författare)
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Trimeric microsomal glutathione transferase 2 displays one third of the sites reactivity
- 2015
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Ingår i: Biochimica et Biophysica Acta - Proteins and Proteomics. - : Elsevier BV. - 1570-9639 .- 1878-1454. ; 1854:1010 Pt A, s. 1365-1371
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Tidskriftsartikel (refereegranskat)abstract
- Human microsomal glutathione transferase 2 (MGST2) is a trimeric integral membrane protein that belongs to the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) family. The mammalian MAPEG family consists of six members where four have been structurally determined. MGST2 activates glutathione to form a thiolate that is crucial for GSH peroxidase activity and GSH conjugation reactions with electrophilic substrates, such as 1-chloro-2,4-dinitrobenzene (CDNB). Several studies have shown that MGST2 is able to catalyze a GSH conjugation reaction with the epoxide LTA(4) forming the pro-inflammatory LTC4. Unlike its closest homologue leukotriene C-4 synthase (LTC4S), MGST2 appears to activate its substrate GSH using only one of the three potential active sites [Ahmad S, et al. (2013) Biochemistry. 52, 1755-1764]. In order to demonstrate and detail the mechanism of one-third of the sites reactivity of MGST2, we have determined the enzyme oligomeric state, by Blue native PAGE and Differential Scanning Calorimetry, as well as the stoichiometty of substrate and substrate analog inhibitor binding to MGST2, using equilibrium dialysis and Isothermal Titration Calorimetry, respectively. Global simulations were used to fit kinetic data to determine the catalytic mechanism of MGST2 with GSH and CDNB (1-chloro-2,4-dinitrobenzene) as substrates. The best fit was observed with 1/3 of the sites catalysis as compared with a simulation where all three sites were active. In contrast to LTC4S, MGST2 displays a 1/3 the sites reactivity, a mechanism shared with the more distant family member MGST1 and recently suggested also for microsomal prostaglandin E synthase-1.
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| 2. |
- Ahmad, Shakeel, et al.
(författare)
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Two-Tone PLL for on-Chip IP3 Test
- 2010
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Ingår i: Swedish System-on-Chip Conference.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Ahmad, T., et al.
(författare)
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Frequency and outcomes of undiagnosed diabetes mellitus in patients presenting with acute myocardial infarction
- 2020
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Ingår i: Medical Forum Monthly. - : Medical Forum Monthly. - 1029-385X. ; 31:12, s. 3-7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To find out frequency and outcomes of undiagnosed diabetes mellitus in patients presenting with acute ST elevation myocardial infarction (STEMI). Study Design: Descriptive / Cross-Sectional Study Place and Duration of study: This study was conducted at the Cardiology Department, Lady Reading Hospital, Peshawar from November 2018 to May 2019. Materials and Methods: Patient of either gender having age ranging between 30-75 years old with acute STEMI who present within 12 hours of symptoms and with no past history of documented diabetes mellitus were included in the study. Venous blood samples for laboratory data, including random blood sugar, two fasting blood sugar and HBA1c using hitachi modular evo p800 machine was done. Results: A total of 158 patients having acute STEMI were studied. Males were 68.4% (n=108).The mean age was 59.65 ±10.80 years. Frequency of undiagnosed diabetes mellitus was 31.64 % (n = 50). In non-diabetics stress hyperglycemia was found in 51.85 % (n=56) patients. Among various types of STEMI, anterior STEMI was more common presentation 34.1 % (n=54. p= 0.85). Mean HBA1C was 6.19 ± 1.87%. Frequency of Ventricular tachycardia (VT) was 22.2 % in which undiagnosed diabetics were n=18 (p=0.004).Ventricular fibrillation was present in 13.3 % patients with undiagnosed diabetics were n=14 (p=0.001). Frequency of AF was 13.9% (n=22) with undiagnosed diabetics having AF in n=13 (p=0.003). SVT was present in 5.7% (n=9) patients with not significant difference between two groups (p=0.017). Among various mechanical complications VSR was present in 10 % (n=16) of patients (p=0.001), cardiogenic shock in 11.1 % (n=18) patients (p=0.004), acute LVF was present in 15.8 % patients (p=0.017). Conclusion: In our study we concluded that one third of patients having acute ST elevation myocardial infarction have undiagnosed diabetes mellitus (31.64 %, n = 50). The most common complication was ventricular tachycardia among electrical complication and LVF among mechanical complication.
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| 4. |
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| 5. |
- Braian, Clara, 1981-
(författare)
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Innate immune responses to Mycobacterium tuberculosis infection : How extracellular traps and trained immunity can restrict bacterial growth.
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the cause of 1.5 million deaths in 2018. During a pulmonary TB infection, the bacterium reaches the lungs and is phagocytosed by cells of the innate immune system, primarily macrophages. The macrophages are either able to eradicate the bacteria or the bacteria start to replicate, and the following immune response leads to the formation of a large cluster of different cell types called a granuloma. In the granuloma the mycobacteria are contained in a latent infection, or they can start to replicate causing rupture of the granuloma and spread of the disease. Neutrophils are also innate immune cells that are rapidly recruited to the site of infection. They are phagocytes, but they also exert extracellular effector mechanisms by their release of microbicidal granule proteins, reactive oxygen species and neutrophil extracellular traps. M. tuberculosis has co-evolved and adapted to the human host making it ingenious at exploiting the human immune response, promoting its survival and replication in human host cells. The human immune system has also evolved mechanisms to limit M. tuberculosisreplication and spread. This thesis covers work on the innate immune response to TB and how neutrophils and macrophages respond to a mycobacterial infection and can control M. tuberculosis-replication.Neutrophils and macrophages can respond to M. tuberculosis by releasing extracellular traps. We demonstrated that neutrophil extracellular traps contain the danger signal heat-shock protein 72 when induced by mycobacteria, which subsequently mediate a proinflammatory activation of adjacent macrophages. Macrophages can also release extracellular traps, and we observed the release of macrophage extracellular traps in response to M. tuberculosis that grow in cord-structures. We further demonstrated that the induction of extracellular traps also required the mycobacterial virulence factor ESAT-6.Trained immunity is an epigenetically regulated memory of the innate immune system that results in a heightened response to a later encounter of the same or different pathogen. β-glucans are structural components of microbial cell walls and known inducers of trained immunity. We studied the effects of β-glucan from a bacterial source (curdlan from Alcaligenes faecalis), from yeast (WGP dispersible from Saccharomyces cerevisiae) and from the supernatant of a multicellular fungi (Alternaria) in search of functional changes in human macrophages which enhanced their anti-mycobacterial capacity. M. tuberculosis growth reduction was observed in WGP dispersible-trained macrophages when co-cultured with neutrophils. We also discovered that the interferon-gamma (IFNγ) signaling pathway, which is important for mycobacterial control, is hypomethylated in the WGP dispersible-trained macrophages. Since hypomethylation of genes typically is associated with gene activation, this suggests a more active IFNγ signaling in response to β-glucan innate immune training.Most of our studies were performed using in vitro culturing of primary human macrophages and neutrophils. However, an in vitro 3D tissue model is a valuable tool when studying complex events that occur during a TB infection that involves both multiple cell types and requires knowledge of the spatial movement of cells. In this thesis we also describe an in vitro lung tissue model, which we could use to observe the clustering of monocytes around mycobacteria and quantify the size and number of macrophage clusters.In conclusion, this thesis comprises work on innate immune functions during tuberculosis infection. We describe extracellular trap formation in macrophages and neutrophils in response to M. tuberculosis. We also explore trained immunity and how β-glucan training can enhance mycobacterial growth restriction.
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| 6. |
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| 7. |
- Aristote, Nkongolo Tshamala, et al.
(författare)
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Methods of improving the initial Coulombic efficiency and rate performance of both anode and cathode materials for sodium-ion batteries
- 2022
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Ingår i: Chinese Chemical Letters. - : Elsevier BV. - 1001-8417 .- 1878-5964. ; 33:2, s. 730-742
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Tidskriftsartikel (refereegranskat)abstract
- Sodium-ion batteries (SIBs) have gained more scientists’ interest, owing to some facts such as the natural abundance of Na, the similarities of physicochemical characteristics between Li and Na. The irreversible Na+ ions consumption during the first cycle of charge/discharge process (due to the formation of the solid electrolyte interface (SEI) on the electrode surface and other irreversible reactions) is the factor that determines high performance SIBs and largely reduces the capacity of the full cell SIBs. Thus, the initial coulombic efficiency (ICE) of SIBs for both anode and cathode materials, is a key parameter for high performance SIBs, and the point is to increase the transport rate of the Na+ ions. Therefore, developing SIBs with high ICE and rate performance becomes vital to boost the commercialization of SIBs. Here we provide a review on the methods to improve the ICE and the rate performance, by summarizing some methods of improving the ICE and rate performance of the anode and cathode materials for SIBs, and end by a conclusion with some perspectives and recommendations.
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| 8. |
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| 9. |
- Bokelmann, L, et al.
(författare)
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Point-of-care bulk testing for SARS-CoV-2 by combining hybridization capture with improved colorimetric LAMP
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1467-
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to contain the spread of SARS-CoV-2 have spurred the need for reliable, rapid, and cost-effective diagnostic methods which can be applied to large numbers of people. However, current standard protocols for the detection of viral nucleic acids while sensitive, require a high level of automation and sophisticated laboratory equipment to achieve throughputs that allow whole communities to be tested on a regular basis. Here we present Cap-iLAMP (capture and improved loop-mediated isothermal amplification) which combines a hybridization capture-based RNA extraction of gargle lavage samples with an improved colorimetric RT-LAMP assay and smartphone-based color scoring. Cap-iLAMP is compatible with point-of-care testing and enables the detection of SARS-CoV-2 positive samples in less than one hour. In contrast to direct addition of the sample to improved LAMP (iLAMP), Cap-iLAMP prevents false positives and allows single positive samples to be detected in pools of 25 negative samples, reducing the reagent cost per test to ~1 Euro per individual.
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