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81.
Smriti Kala Nichole Cumby Paul D. Sadowski Batool Zafar Hyder Voula Kanelis Alan R. Davidson Karen L. Maxwell 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(16):6022-6027
The genome packaging reactions of tailed bacteriophages and herpes viruses require the activity of a terminase enzyme, which is comprised of large and small subunits. Phage genomes are replicated as linear concatemers composed of multiple copies of the genome joined end to end. As the terminase enzyme packages the genome into the phage capsid, it cleaves the DNA into single genome-length units. In this work, we show that the phage HK97 HNH protein, gp74, is required for the specific endonuclease activity of HK97 terminase and is essential for phage head morphogenesis. HNH proteins are a very common family of proteins generally associated with nuclease activity that are found in all kingdoms of life. We show that the activity of gp74 in terminase-mediated cleavage of the phage cos site relies on the presence of an HNH motif active-site residue, and that the large subunit of HK97 terminase physically interacts with gp74. Bioinformatic analysis reveals that the role of HNH proteins in terminase function is widespread among long-tailed phages and is uniquely required for the activity of the Terminase_1 family of large terminase proteins.Tailed bacteriophages and herpes viruses package their large double-stranded DNA genomes into a preformed protein shell, known as the “prohead,” using terminase enzymes. In both types of viruses, the genome is synthesized as concatemers composed of multiple copies of the genome joined end to end. This concatemeric DNA is packaged into the prohead and cleaved into genome-length units by terminase in an ATP-dependent reaction. Phage terminases are composed of two proteins: the large subunit harbors an endonuclease domain and an ATPase that powers the DNA packaging reaction, and the small subunit mediates specific DNA-binding required for recognition of packaging sites in the phage genome. A variety of elegant structural and biophysical studies have recently provided insight into the molecular mechanisms of terminase function (1, 2). However, the factors that affect the action of terminase enzymes in vivo have been less well characterized.Terminase enzymes perform several functions. They specifically recognize and bind the viral genome, interact with the prohead, then drive the DNA into the head through the narrow entry channel formed by the portal protein that is positioned at a single vertex of the head. During this process terminases also cleave the viral DNA, either nonspecifically upon head filling or at a specific site known as “cos.” The efficient packaging of a phage genome in vivo may require phage-encoded cofactors in addition to the terminase enzyme. For example, Escherichia coli phage λ gpFI facilitates interaction of the terminase–DNA complex with proheads (3–6). A wide variety of phages appear to encode proteins with a function similar to λ gpFI (7). Additionally, the activity of Bacillus subtilis phage phi29 terminase requires a phage-encoded RNA molecule bound to its portal protein (8), and in vivo packaging of the E. coli phage T4 genome can only be completed with the participation of the phage-encoded endonuclease, gp49 (9). The general prevalence and importance of terminase cofactors is difficult to evaluate because few studies have addressed this issue.We recently reported that phage genomes often encode proteins possessing an HNH motif near their terminase genes (10). The HNH motif is ∼35 aa long, and is characterized by the presence of two highly conserved His residues and one Asn residue. These HNH motifs, as defined by the large (∼7,400-member) HNH Pfam (11) protein sequence family (PF01844), are often found in proteins that possess endonuclease activity, such as site-specific homing endonucleases (12, 13), colicins (14, 15), S pyocins (16), and restriction enzymes (17–19). HNH motif-containing proteins comprised of primarily an HNH motif as found in E. coli colicins, usually possess nonspecific endonuclease activity. Conversely, HNH motif-containing proteins may contain DNA-recognition domains in addition to the HNH motif and thus possess high sequence specificity, as found in the homing endonucleases.The frequent juxtaposition of HNH and phage terminase genes (10, 20) suggests a unique role for HNH proteins in the endonuclease and/or packaging activities of the terminases. To address this issue, we investigated the function of E. coli phage HK97 gp74, a 119-residue protein containing an HNH motif. The gene encoding gp74 is located at the extreme 3′ end of the mature linear HK97 genome, adjacent to the cos site. In both the lysogen and replicative form of the HK97 genome gene 74 is immediately adjacent to genes 1 and 2, which encode the small and large subunits of terminase (TerS and TerL), respectively. Whereas gp74 was previously found to possess endonuclease activity (10), its role in the HK97 replication cycle remained uncharacterized. In this study we used functional and bioinformatic analyses to investigate its function. 相似文献
82.
Soha M. Abd El Dayem Hala Hamza Sohair Helal Azza Mohamed Heba Hassan 《Indian heart journal》2014,66(6):745-750
Objective
We evaluated the effectiveness of long acting penicillin (LAP) as a 2-weekly regimen in winter and a 3-weekly regimen in summer for prevention of streptococcal colonization and also studied the common complaints of patients during the period of compliance for LAP administration. We also attempted to determine the incidence of relapses or recurrence of rheumatic fever (RF) after the onset of first episode of RF.Patients & methods
210 rheumatic patients with good compliance to LAP (for at least one year) were included in the study. Demographic, clinical information, patients'' complaints and echocardiographic data of rheumatic patients were collected both retrospectively and prospectively. Anti-streptolysin O titre (ASOT) and throat swab culture were done at the end of the study (on Day 14 in the 2-weekly regimen and on Day 21 in the 3-weekly regimen).Results
The age of onset of rheumatic fever was mostly between 5 and 15 years and the youngest patient was 2 years old. Subclinical carditis (SCC) was present in 79 (37%) of all the patients in the study population. Only 7 patients (3.3%) had a relapse within 2 years of the acute episode of RF. At the end of the study, ASOT was found to be high only in 11 patients (5.2%) and throat swab cultures were found negative in all patientsConclusion
LAP regimen is fairly effective in eradicating streptococcal colonization. The incidence of relapse of RF within 2 years of the acute episode of RF is relatively low. 相似文献83.
Mark Mills Elizabeth Johnson Hamza Zafar Andrew Horwood Nicola Lax Sarah Charlesworth Anna Gregory Justin Lee Jonathan Sahu Graeme Kirkwood Nicholas Kelland Andreas Kyriacou 《The British Journal of Cardiology》2020,27(2)
There is increasing evidence for the role of exercise-based cardiac rehabilitation in the management of patients with atrial fibrillation (AF). However, this intervention has not yet been widely adopted within the National Health Service (NHS).We performed a feasibility study on the utilisation of an established NHS cardiac rehabilitation programme in the management of AF, and examined the effects of this intervention on exercise capacity, weight, and psychological health. We then identified factors that might prevent patients from enrolling on our programme.Patients with symptomatic AF were invited to participate in an established six-week exercise-based cardiac rehabilitation programme, composed of physical activity and education sessions. At the start of the programme, patients were weighed and measured, performed the six-minute walk test (6MWT), completed the Generalised Anxiety Disorder Questionnaire (GAD-7), and the Patient Health Questionnaire (PHQ-9). Measurements were repeated on completion of the programme.Over two years, 77 patients were invited to join the programme. Twenty-two patients (28.5%) declined participation prior to initial assessment and 22 (28.5%) accepted and attended the initial assessment, but subsequently withdrew from the programme. In total, 33 patients completed the entire programme (63.9 ± 1.7 years, 58% female). On completion, patients covered longer distances during the 6MWT, had lower GAD-7 scores, and lower PHQ-9 scores, compared with their baseline results. Compared with patients that completed the entire programme, those who withdrew from the study had, at baseline, a significantly higher body mass index (BMI), covered a shorter distance during the 6MWT, and had higher PHQ-9 and GAD-7 scores.In conclusion, enrolling patients with AF into an NHS cardiac rehabilitation programme is feasible, with nearly half of those invited completing the programme. In this feasibility study, cardiac rehabilitation resulted in an improved 6MWT, and reduced anxiety and depression levels, in the short term. Severe obesity, higher anxiety and depression levels, and lower initial exercise capacity appear to be barriers to completing exercise-based cardiac rehabilitation. These results warrant further investigation in larger cohorts.Key words: atrial fibrillation, cardiac rehabilitation, National Health Service 相似文献
84.
Abdul Qayoom Mugheri Aneela Tahira Umair Aftab Muhammad Ishaq Abro Arfana Begum Mallah Gulam Zuhra Memon Humaira Khan Mazhar Ali Abbasi Imran Ali Halepoto Saleem Raza Chaudhry Zafar Hussain Ibupoto 《RSC advances》2019,9(59):34136
The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy. In this study, we developed a facile approach to produce porous carbon from the dehydration of sucrose and use it for the preparation of nanocomposites with cobalt oxide (Co3O4). The nanocomposites were studied by the powder X-ray diffraction and scanning electron microscopy techniques, and they exhibited the cubic phase of cobalt oxide and porous structure of carbon. The nanocomposites showed significant OER activity in alkaline media, and the current densities of 10 and 20 mA cm−2 could be obtained at 1.49 and 1.51 V versus reversible hydrogen electrode (RHE), respectively. The impedance study confirms favorable OER activity on the surface of the prepared nanocomposites. The nanocomposite is cost-effective and can be capitalized in various energy storage technologies.The design of efficient nonprecious catalysts for the hydrogen evolution reaction (HER) or the oxygen evolution reaction (OER) is a necessary, but very challenging task to uplift the water-based economy. 相似文献
85.
Taghrid M. Gaafar Hala A. Abdel Rahman Wael Attia Hala S. Hamza Konrad Brockmeier Rabab E. El Hawary 《Clinical and experimental medicine》2014,14(2):177-184
Adult peripheral blood contains a limited number of endothelial progenitor cells that can be isolated for treatment of ischemic diseases. The adipose tissue became an interesting source of stem cells for regenerative medicine. This study aimed to investigate the phenotype of cells obtained by culturing adipose-derived mesenchymal stem cells (ad-MSCs) in the presence of endothelial growth supplements compared to endothelial cells obtained from umbilical cord blood (UCB). Passage 3 ad-MSCs and mononuclear layer from UCB were cultured in presence of endothelial growth media for 3 weeks followed by their characterization by flow cytometry and polymerase chain reaction. After culture in endothelial inductive media, ad-MSCs expressed endothelial genes and some endothelial marker proteins as CD31 and CD34, respectively. Adipose tissue could be a reliable source for easy obtaining, expanding and differentiating MSCs into endothelial-like cells for autologous cell-based therapy. 相似文献
86.
Three novel Schiff bases, namely N-(4-((4-((phenylimino)methyl)phenoxy)methoxy)benzylidene)benzenamine (UA), N-(3-methoxy-4-((2-methoxy-4-((phenylimino)methyl)phenoxy)methoxy)benzylidene)benzenamine (UB), and N-(3-ethyl-4-((2-ethyl-4-((phenylimino)methyl)phenoxy)methoxy)benzylidene)benzenamine (UC), were synthesized and their structures were elucidated through diverse spectroscopic techniques such as FT-IR, GC-MS, 1H NMR and 13C NMR. The corrosion inhibition effect of these Schiff bases on aluminum alloy AA2219-T6 in acidic medium was explored using weight loss, Tafel polarization, and electrochemical impedance spectroscopy. Theoretical quantum chemical calculations using density functional theory were employed to determine the adsorption site. It was found that inhibition efficiencies increase with an increase in the inhibitor concentration. Tafel plots showed that these Schiff bases function as mixed inhibitors. Adsorption of the Schiff bases on aluminum followed the Langmuir adsorption isotherm and the value of showed a dominant chemical mechanism. FT-IR and SEM techniques were used to investigate the surface morphology. The compounds showed a substantial corrosion inhibition for aluminum alloy in 0.1 M HCl at 298 K. UB and UC exhibited superior anticorrosion efficiency compared to UA originating from the electron-donating methoxy and ethoxy group substitutions, respectively. There was found to be good correlation between molecular structure and inhibition efficiencies.Novel Schiff bases characterized through spectroscopic techniques and used as anticorrosive agents for aluminium alloy acidic medium. Electrochemical techniques and DFT studies were used to study inhibition effect and molecular interactions. 相似文献
87.
88.
Mohsin Ali Khan Furqan Farooq Mohammad Faisal Javed Adeel Zafar Krzysztof Adam Ostrowski Fahid Aslam Seweryn Malazdrewicz Mariusz Malak 《Materials》2022,15(1)
To avoid time-consuming, costly, and laborious experimental tests that require skilled personnel, an effort has been made to formulate the depth of wear of fly-ash concrete using a comparative study of machine learning techniques, namely random forest regression (RFR) and gene expression programming (GEP). A widespread database comprising 216 experimental records was constructed from available research. The database includes depth of wear as a response parameter and nine different explanatory variables, i.e., cement content, fly ash, water content, fine and coarse aggregate, plasticizer, air-entraining agent, age of concrete, and time of testing. The performance of the models was judged via statistical metrics. The GEP model gives better performance with R2 and ρ equals 0.9667 and 0.0501 respectively and meet with the external validation criterion suggested in the previous literature. The k-fold cross-validation also verifies the accurateness of the model by evaluating R2, RSE, MAE, and RMSE. The sensitivity analysis of GEP equation indicated that the time of testing is the influential parameter. The results of this research can help the designers, practitioners, and researchers to quickly estimate the depth of wear of fly-ash concrete thus shortening its ecological susceptibilities that push to sustainable and faster construction from the viewpoint of environmentally friendly waste management. 相似文献
89.
90.