214 research outputs found
The Dimerization Interface in VraR is Essential to Induction of the Cell Wall Stress Response in Staphylococcus aureus: A potential Druggable Target
Background
Staphylococcus aureus remains a medical challenge in the treatment of bacterial infections. It has acquired resistance to commonly used antibiotics, and to those considered to be the last weapons in treating staphylococcal infections, such as vancomycin. Studies have revealed that S. aureus is capable of mounting a rapid response to antibiotics that target cell wall peptidoglycan biosynthesis, such as β-lactams and vancomycin. The two-component system VraSR has been linked to the coordination of this response. VraS is a histidine kinase that undergoes autophosphorylation in the presence of signals elicited upon cell wall damage and it then transfers its phosphoryl group to VraR. VraR is a response regulator protein that functions as a transcription factor. Phosphorylation of VraR leads to its dimerization, which is required for optimum binding to its target promoters. Two-component systems have been targeted for the development of antibacterial agents. Deletion of the vraS or vraR gene has been shown to re-sensitize S. aureus to β-lactams and vancomycin.
Results
In this study, we explored perturbation of the VraR phosphorylation-induced activation as a means to inhibit the VraSR-mediated signal transduction pathway. We show that dimerization of VraR is essential for the phosphorylation-induced activation of VraR. A single point mutation in the dimerization interface of VraR, in which Met13 was replaced by Ala, led to the inability of VraR to dimerize and to bind optimally to the target promoter. The consequences of these in vitro molecular deficiencies are equally dramatic in vivo. Complementation of a vraR deletion S. aureus strain with the vraRM13Ala mutant gene failed to induce the cell wall stress response.
Conclusions
This study highlights the potential of targeting the phosphorylation-induced dimerization of VraR to disrupt the S. aureus cell wall stress response and in turn to re-sensitize S. aureus to β-lactams and vancomycin.York University Librarie
Implementation of the systemic approach in teaching and learning biochemistry in Albania
Though newly introduced, global education has occupied a special place in the glossary of teaching. It props up both the teachers and students to have a broad view of the problems and issues and think constructively of the future and their role in modeling it. In this respect, teachers need to consider themselves as global citizens and take all the responsibilities that accompany the phenomenon of globalism. At the same time, teachers must regard themselves as members of their community. The main characteristic of teaching in the framework of global education is the partnership between the teacher and the student which finds itself expressed in the methods and numerous interactive techniques and constitutes its content. The teachers who keep teaching by employing traditional methods find it difficult to promote the active role of the students in the classroom, see the relationship of their subject they are teaching with others, and perceive the prospective of their teaching. The philosophy of global teaching integrates exactly those elements which the traditional method lacks. The focus of the philosophy of global education is the student and teaching. These days we live in a society which is constantly becoming essentially globalized and fundamentally affected by both decisions made irrespective of our will and events that take place far from us. Consequently, we are constantly under the pressure of global, cultural, social, economic, technologic, and environmental tendencies as well as changes which come about very rapidly. Therefore, it is our duty and that of the entire society to increase students’ ability to think systematically in order that they could be able to face this ever globalizing world, think constructively of their future and the role they are to play to shape it, and learn from the past. Methodology provides students and lecturers with a global image of the teaching of science. As is known, teaching is carried out through communication. Teaching all over the world is adopting this method. Learning process becomes pleasant if better communication skills of the teacher prevail upon the inherent inertia associated with the students, while they focus upon a difficult subject. This way of teaching is increasingly being highly appraised by the world academy
ON SEVERAL STYLISTIC PROCREATIONS OF THE GHEG VARIETY OF ALBANIAN
In this paper we intend to present several stylistic procreations, as expressions of various colorations, which have a certain importance in Gheg variety of Albanian and constitute an extraordinary example, not only in Ethnolinguistics, but also in shaping the features of the style of Gheg variety of Albanian, revealing as much as possible the contribution in Stylistics. Such procreations are: 1. Diminutives, with a significant importance with affectionate suffixes, such as: –ush(ë) in common nouns as: zemrush, bukurushë and proper nouns as Gjushi, Lushi. 1.2. Affectionate suffixes –losh, as: tatalosh. 1.3. New word forms, with affectionate suffixes: –z/ë (for feminine nouns) and –th (for masculine nouns): derëzën, rremtha. -lat, -llat (for plural): gjethlat; tingllat; -aç,-uc, uqe, -icë (with pejorative meaning): turulluqe, budallicë, garravaç etc. 2. Onomatopoeic words that serve as parts of a sentence: të kekllishunit; trokllimi; 3. Exclamations and elements of affirmation with exclamatory element, as: Ele; Hê; Palé, etc. Solid compound words as exclamations: Pash besën!, Pasha bukën!, Ç’â zâni lum miku? 4. Damnations and expressions of “të truarit”, as: He paç vetin n’qafë!; Mos e prûsh kryet! Such occurrences indicate a rich variety, with a particular style, with a discourse tinged with personal figurative elements, originating from areas of northern Albania
Systemic objective test in medical biochemistry: Part 1-metabolism of carbohydrates
A very important element of the teaching plan is students’ assessment. Assessment should be very objective and backed up with feedback. A necessary condition for this type of evaluation is the formation of questions. The questions should lead the thinking process of the students with skills and clarity of thought. In this way, these questions will serve as clear ideas and help to develop the imagination and the research. Such innovation provides systematic evaluation, which is based on systematic diagram. Testing plays an important role in this system. The objective test is created in a way that a different estimator that assesses independently will achieve the same results for the introduced level of knowledge and abilities based on true answers. In comparison with the traditional objective test, the systemic objective test includes many demands that are completely structured; it covers a huge part of the educational schedule, and measures high levels of education (synthesis, analysis and estimation). In this article, we will introduce STFQs, SMCQs, SSQs, SSQs, ASQs, and SCQs as examples of the systemic objective test in medical biochemistry
Systemic approaches to teaching and learning a module of Biochemistry [SATL-BC]
In this article, we introduce the application of SATL in the subject of medical biochemistry. The strategy of this method is based on the collection, organization, and presentation of the map of concepts through the interactive system in the module of which the relations between the concepts and issues will be clarified. The main structural element of the SATL is the systemic diagram which bears all the attributes of a closed concept map. The systemic diagrams are created on the basis of the combination of the concepts that students already have and what they acquire through the study of the modules. The construction of systemic diagram helps students to understand the conceptual framework of the subject. Through the application of systemic methodology, students will study not only concepts, principles, and various metabolic procedures that occur in the organism they will also understand the vital role of biochemistry in medicine and how biochemistry principles are applied in everyday professional practices.[AJCE, 3(1), January 2013
Othello in the Balkans: Performing Race Rhetoric on the Albanian Stage
This essay examines the racialized rhetoric in Fan Noli’s 1916 Othello translation and the racialized performance techniques employed in A.J. Ricko’s 1953 National Theatre of Albania production. Hoping to combat racial discrimination in Albania, Noli’s translation of Othello renders the Moor an exceptional Turk whose alienation in Venice was designed to mirror the Albanophobic experiences of Albanian immigrants. Moreover, the Albanian Othello can serve as a platform for addressing ethno-racial tensions between Albanians and Turks, northern and southern Albanians, and Albanians of color and white Albanians. Both Noli and Ricko believed there was an anti-racist power inherent within Shakespeare’s play. In the end, however, the race-based rhetoric in the Albanian language, the use of blackface make-up in performance, and the logic and rhetoric of Shakespeare’s play itself challenged these lofty goals for race-healing
Use of Biochemical Markers in Predictive and Diagnostic Means in Diagnosing Obstetrical Pathologies in Albania
Background: The majority of published scientific papers concerning the role of biochemical markers of first trimester such as PAPP-A and free-ß-hCG in predicting future pregnancy complications enhance the importance of these parameters. Objective: To evaluate the role of biochemical markers parameters in other pregnancy disorders after first trimester such as Fetal Growth Restriction, Preeclampsia, Preterm Birth, Stillbirth, Fetal Macrosomia. Materials and methods: As a part of a prospective study, we did study 866 patients that were followed from the beginning of pregnancy to delivery, after giving their agreement. Quantity and quality research methods were used and data was analyzed by IBM SPSS Statistics. Results: Our data of showed that 11.4% of this cohort presented one of the above respective pathologies. The risk was better related to MoM PAPP-A than free-ß-hCG. Patients with MoM PAPP-A less than cut off 0.5, has double risk of having the pathology comparing to those patients with Conclusions: Consequently, the value of counseling the patient so early, with the information taken from evidence based medicine, has importance for them, in order to be more careful after having the results, and make regular control with their physician. Keywords: Biochemical markers, pregnancy complications, Down syndrome
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