| 1. |
- Aljabali, Alaa A. A., et al.
(author)
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The viral capsid as novel nanomaterials for drug delivery
- 2021
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In: Future Science OA. - : Future Science Ltd. - 2056-5623. ; 7:9
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Research review (peer-reviewed)abstract
- The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging. Lay abstract: The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging. Here we performed a comprehensive database search to review findings in this area, demonstrating that viral nanostructures possess unique properties that make them ideal for applications in diagnostics, cell labeling, contrasting agents and drug delivery structures.
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| 2. |
- Carvalho, Lara, et al.
(author)
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Performance of a pellet boiler fired with agricultural fuels
- 2013
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In: Applied Energy. - : Elsevier BV. - 0306-2619 .- 1872-9118. ; 104, s. 286-296
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Journal article (peer-reviewed)abstract
- The increasing demand for woody biomass increases the price of this limited resource, motivating the growing interest in using woody materials of lower quality as well as non-woody biomass fuels for heat production in Europe. The challenges in using non-woody biomass as fuels are related to the variability of the chemical composition and in certain fuel properties that may induce problems during combustion. The objective of this work has been to evaluate the technical and environmental performance of a 15 kW pellet boiler when operated with different pelletized biomass fuels, namely straw (Triticum aestivum), Miscanthus (Miscanthus × giganteus), maize (Zea mays), wheat bran, vineyard pruning (from Vitis vinifera), hay, Sorghum (Sorghum bicolor) and wood (from Picea abies) with 5% rye flour. The gaseous and dust emissions as well as the boiler efficiency were investigated and compared with the legal requirements defined in the FprEN 303-5 (final draft of the European standard 303-5). It was found that the boiler control should be improved to better adapt the combustion conditions to the different properties of the agricultural fuels. Additionally, there is a need for a frequent cleaning of the heat exchangers in boilers operated with agricultural fuels to avoid efficiency drops after short term operation. All the agricultural fuels satisfied the legal requirements defined in the FprEN 303-5, with the exception of dust emissions during combustion of straw and Sorghum. Miscanthus and vineyard pruning were the best fuels tested showing comparable emission values to wood combustion.
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| 3. |
- Jackson, Alice M., et al.
(author)
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Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
- 2020
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In: Circulation. - 1524-4539. ; 142:11, s. 1040-1054
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Journal article (peer-reviewed)abstract
- BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide $<$40, 40, and $>$40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on $<$40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking $>$40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow- up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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| 4. |
- Kamran, Mohammad, et al.
(author)
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Helicobacter pylori shows asymmetric and polar cell divisome assembly associated with DNA replisome
- 2018
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In: The FEBS Journal. - : WILEY. - 1742-464X .- 1742-4658. ; 285:13, s. 2531-2547
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Journal article (peer-reviewed)abstract
- DNA replication and cell division are two fundamental processes in the life cycle of a cell. The majority of prokaryotic cells undergo division by means of binary fission in coordination with replication of the genome. Both processes, but especially their coordination, are poorly understood in Helicobacter pylori. Here, we studied the cell divisome assembly and the subsequent processes of membrane and peptidoglycan synthesis in the bacterium. To our surprise, we found the cell divisome assembly to be polar, which was well-corroborated by the asymmetric membrane and peptidoglycan synthesis at the poles. The divisome components showed its assembly to be synchronous with that of the replisome and the two remained associated throughout the cell cycle, demonstrating a tight coordination among chromosome replication, segregation and cell division in H. pylori. To our knowledge, this is the first report where both DNA replication and cell division along with their possible association have been demonstrated for this pathogenic bacterium.
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| 5. |
- Nitharwal, Ram G., et al.
(author)
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DNA binding activity of Helicobacter pylori DnaB helicase : the role of the N-terminal domain in modulating DNA binding activities
- 2012
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In: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 279:2, s. 234-250
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Journal article (peer-reviewed)abstract
- Replicative helicases are major motor proteins essential for chromosomal DNA replication in prokaryotes. Usually hexameric in solution, their DNA binding property must have different roles at stages ranging from the loading onto a branched structure at initiation from the origin to the highly processive translocation during elongation. Here, we have analysed the DNA binding activity of Helicobacter pylori (Hp) replicative helicase, DnaB. The results indicate that while the C-terminal region is important for its DNA binding activity, the N-terminus appears to dampen the proteins affinity for DNA. The masking activity of the N-terminus does not require ATP or hexamerization of HpDnaB and can be overcome by deleting the N-terminus. It can also be neutralized by engaging the N-terminus in an interaction with a partner like the C-terminus of DnaG primase. The inhibitory effect of the N-terminus on DNA binding activity is consistent with the 3D homology model of HpDnaB. Electron microscopy of the HpDnaBssDNA complex showed that HpDnaB preferentially bound at the ends of linear ssDNA and translocated along the DNA in the presence of ATP. These results provide an insight into the stimulatory and inhibitory effects of different regions of HpDnaB on DNA binding activities that may be central to the loading and translocation functions of DnaB helicases.
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| 6. |
- Nitharwal, Ram Gopal, et al.
(author)
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Helicobacter pylori chromosomal DNA replication : Current status and future perspectives
- 2011
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In: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 585:1, s. 7-17
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Research review (peer-reviewed)abstract
- Helicobacter pylori causes gastritis, gastric ulcer and gastric cancer. Though DNA replication and its control are central to bacterial proliferation, pathogenesis, virulence and/or dormancy, our knowledge of DNA synthesis in slow growing pathogenic bacteria like H. pylori is still preliminary. Here, we review the current understanding of DNA replication, replication restart and recombinational repair in H. pylori. Several differences have been identified between the H. pylori and Escherichia coli replication machineries including the absence of DnaC, the helicase loader usually conserved in gram-negative bacteria. These differences suggest different mechanisms of DNA replication at initiation and restart of stalled forks in H. pylori.
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| 7. |
- Petrie, Mark C, et al.
(author)
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Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes.
- 2020
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In: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 323:14, s. 1353-1368
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Journal article (peer-reviewed)abstract
- Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction=.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction=.72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.ClinicalTrials.gov Identifier: NCT03036124.
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| 8. |
- Serenelli, Matteo, et al.
(author)
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Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
- 2020
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In: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:36, s. 3402-3418
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Journal article (peer-reviewed)abstract
- Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).Key inclusion criteria were: New York Heart Association Class II-IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110mmHg; 981≥110<120; 1149≥120<130; and 1409≥130mmHg. The placebo-corrected reduction in SBP from baseline to 2weeks with dapagliflozin was -2.54 (-3.33 to -1.76) mmHg (P<0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome [20.6, 95% confidence interval (95% CI) 17.6-24.2] than those in the highest SBP category (13.8, 11.7-16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60-0.97), 0.76 (0.57-1.02), 0.81 (0.61-1.08), and 0.67 (0.51-0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.ClinicalTrials.gov NCT03036124.
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| 9. |
- Sharma, Atul, et al.
(author)
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Intracellular Locations of Replication Proteins and the Origin of Replication during Chromosome Duplication in the Slowly Growing Human Pathogen Helicobacter pylori
- 2014
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In: Journal of Bacteriology. - 0021-9193 .- 1098-5530. ; 196:5, s. 999-1011
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Journal article (peer-reviewed)abstract
- We followed the position of the replication complex in the pathogenic bacterium Helicobacter pylori using antibodies raised against the single-stranded DNA binding protein (HpSSB) and the replicative helicase (HpDnaB). The position of the replication origin, oriC, was also localized in growing cells by fluorescence in situ hybridization (FISH) with fluorescence-labeled DNA sequences adjacent to the origin. The replisome assembled at oriC near one of the cell poles, and the two forks moved together toward the cell center as replication progressed in the growing cell. Termination and resolution of the forks occurred near midcell, on one side of the septal membrane. The duplicated copies of oriC did not separate until late in elongation, when the daughter chromosomes segregated into bilobed nucleoids, suggesting sister chromatid cohesion at or near the oriC region. Components of the replication machinery, viz., HpDnaB and HpDnaG (DNA primase), were found associated with the cell membrane. A model for the assembly and location of the H. pylori replication machinery during chromosomal duplication is presented.
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| 10. |
- Verma, Vijay, et al.
(author)
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Modulation of the enzymatic activities of replicative helicase (DnaB) by interaction with Hp0897 : a possible mechanism for helicase loading in Helicobacter pylori
- 2016
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 44:7, s. 3288-3303
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Journal article (peer-reviewed)abstract
- DNA replication in Helicobacter pylori is initiated from a unique site (oriC) on its chromosome where several proteins assemble to form a functional replisome. The assembly of H. pylori replication machinery is similar to that of the model gram negative bacterium Escherichia coli except for the absence of DnaC needed to recruit the hexameric DnaB helicase at the replisome assembly site. In the absence of an obvious DnaC homologue in H. pylori, the question arises as to whether HpDnaB helicase is loaded at the Hp-replication origin by itself or is assisted by other unidentified protein(s). A high-throughput yeast two-hybrid study has revealed two proteins of unknown functions (Hp0897 and Hp0340) that interact with HpDnaB. Here we demonstrate that Hp0897 interacts with HpDnaB helicase in vitro as well as in vivo. Furthermore, the interaction stimulates the DNA binding activity of HpDnaB and modulates its adenosine triphosphate hydrolysis and helicase activities significantly. Prior complex formation of Hp0897 and HpDnaB enhances the binding/loading of DnaB onto DNA. Hp0897, along with HpDnaB, colocalizes with replication complex at initiation but does not move with the replisome during elongation. Together, these results suggest a possible role of Hp0897 in loading of HpDnaB at oriC.
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| 11. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 12. |
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| 13. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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