Transcriptional and translational inhibitors block serotonergic phase advances of the SCN circadian pacemaker in vitro

The mammalian circadian pacemaker is located in the suprachiasmatic nucleus (SCN). Phase shifts of the pacemaker are modulated by various inputs. The input that we investigated is the serotonergic (5HT) input from the raphe nuclei. 5HT phase-advances the SCN pacemaker when applied during mid-subjective day. In vitro studies indicate that 5HT phase-advances the mammalian circadian pacemaker through a process that includes stimulation of 5-HT7 receptors, activation of protein kinase A, and opening of K+ channels. How these cytoplasmic and membrane events translate into a shift in the molecular core of the circadian oscillator is not known. To further understand this process, we investigated whether serotonergic phase advances require protein synthesis. Using two reversible translational inhibitors, anisomycin and cycloheximide, we show that inhibition of protein synthesis blocks SHTergic phase shifts. We further show that a transcriptional inhibitor, 5,6-dichloro-l-P-ribobenzimidazole (DRB), also blocks the SHTergic phase shifts in the SCN circadian pacemaker. These results are similar to those found previously with respect to 5HTergic modulation of the Aplysia ocular circadian clock, and suggest that 5HT may phase-shift the SCN pacemaker through increasing transcription and translation of specific proteins

COMPARATIVE ADVANTAGES OF WINE IN FUNCTION OF TERRITORIAL MARKETING STRATEGY

In this paper the analysis is focused on the marketing component as an element of economic cohesion and diversity, whose main purpose is to proclaim priority values for the society that need to be realized. Well-conceived and implemented territorial marketing strategy is the basis for sustainable regional development that resolves in well-being of the actors who live on that territory, economic growth and development of the region, recognisability and interest by non-residents of the territory. In order to present directions for establishing a system for promoting territorial attractiveness and the specifics it offers, a set of methodological tools has been applied in the paper to determine whether the comparative advantage of the country is really directed toward the production of wine or there is a need for change in the strategic approach according to the needs and requirements of the international market. Comparative analysis is presented through quantitative assessment using the Balassa index, while the inductive analysis determines the directions and recommendations for a territorial marketing strategy. Based on the calculated results, several directions for potential marketing affirmation are presented, as well as redesigning or directing the recognition of the territory to the service sector in combination with the agricultural specifics that it possesses. The goal is to raise the potential of the service sector through the activation of potentials in the domain of propulsive ICT service that can shape the future profile of the territory in the direction of products with increased added value

MARKETING ACTIVITIES AND SALES OF MACEDONIAN WINERIES IN A CONDITION OF PANDEMIC COVID-19

Covid-19 has implications on the overall operation of Macedonian wineries and directly affected the decline in domestic sales and export to international markets. The HORECA sector stopped working completely or partially in all countries. The crisis affected the partial or total cuts of marketing costs, by postponing or canceling planned projects. The wineries failed to sell the planned quantities and were forced to make significantly lower purchases for the 2020 harvest than in previous years. The paper presents a large number of data received from the Association Wines of Macedonia,  Customs Office of the Republic of North Macedonia, Ministry of Agriculture, Forestry and Water Economy of the Republic of North Macedonia, State Inspectorate for Agriculture, Internet articles containing topics relevant to the research. The additional data presented were collected from Macedonian wineries through a questionnaire on operations during the corona crisis. This paper provides an overview of the problems faced by Macedonian wineries during the corona crisis in terms of marketing and sales, primarily in international markets and analyzes the declined average price and reduced investment in marketing.   Key words: North Macedonia, Macedonian wineries, Covid-19, implications, marketing, win

The Challenge of 21st Century Leadership: The Transition from "I" to "We"

The exponential growth of science, in all spheres of modern life, is a big challenge forevery person, in order to find a way to follow these changes. The belief in theeconomy, politics, leading elites, as well as in the media is probably at the lowestpossible level, not only nationally and regionally, but also globally. Using differentcommunication channels (like social networks as the simplest communicationchannels) each stakeholder can give negative reviews and comments about anorganization. In such difficult and challenging business conditions, the usual methodsand theories of management do not work best at all levels of cooperation and action.The reason for this probably lies in the fact that while the world is changing rapidly,transforming itself into new forms, management as a science fails to follow in parallel,the steps of all the changes and processes caused by globalization. The competitionfor talents in the labor market today, requires additional effort from the managementof organizations. If we take into account that fact (from many others), we can clearlysee that a "new" time is coming in which managers need to be constantly(re)inventive, both in terms of themselves, as a person, but also in term of managingtheir organizations, too. For those who want to create the necessary change and adaptto modern functioning, this "journey" can be a significant evolution on an individual,collective and global level filled with many innovations and challenges. The pandemicthat brought a major crisis situation at all levels, on the other hand, led to changes inthe management methodology. All these crisis situations put the leaders to a hugetest to prove, which of them is the real manager in bad times so as in good times, andwhich remains even a step behind or down, because he cannot face the challengesfirst as a person himself, and then on the other hand to adapt the employees to thenewly imposed working conditions, without disturbing the humanitarian aspect. The"new" time proved to be a time of significant changes that dictate a different culture ofliving, different experiencing things, re-examining all the trends that are aimed at akind of growth and development of the person, that steps with enormous speedthrough all changes and processes, as a being, a person, a motivator, an innovator, amanager, to finally realize that until the "I" didn’t turns into the "WE", we cannot talkabout any leadership, in context of all the challenges, that only the right manager canface every day

Улогата на возраста врз развојот на говорот кај субјекти со кохлеарни импланти

The cochlear implant has been approved as a method of treating bilateral deep deafness since the 1980s, and since then candidate selection methods have changed several times. Initially, the candidates were only adult patients, and in 1990 the cochlear implant was approved for the first time in children under 2 years of age by the US Food and Drug Administration. In 2000, the same US Administration reduced the limit to one year. The aim of this study was to determine the effect of age at cochlear implantation on speech recognition abilities. Concerning the age groups in which the subjects were assigned to, the best results on the tests were achieved by the group who underwent cochlear implantation at the youngest age. In conclusion, the benefit from cochlear implant in subjects with pre-lingual hearing impairment of the most severe degree has to be stressed and it is much bigger in comparison to individual amplifying hearing aids. If cochlear implant is placed at the youngest age, the results might lead to even 100% of active involvement in the social life of individuals with this kind of impairment.Кохлеарниот имплант е одобрен како метод за лекување на билатералната длабока глувост уште од осумдесеттите години, а оттогаш методите на селекција на кандидатите се менувале повеќе пати. Најпрво кандидати биле само возрасни пациенти, а во 1990 година за прв пат се одобрил кохлеарниот имплант и кај деца со најмалку наполнети 2 години  живот, од страна на Американската администрација за храна и лекови. Во 2000 година истата Американска администрација го намалила лимитот на една година. Целта на ова истражување беше да се утврди влијанието на возраста при вградувањето на кохлеарниот имплант врз успешноста на говорниот развој. Во однос на возрасната група според која испитаниците беа поделени, најдобри резултати покажа групата кај која имплантацијата беше направена на најмала возраст. Во заклучокот сакаме да потенцираме дека бенефитот од кохлеарниот имплант кај лицата со прелингвално слушно оштетување со најтежок степен е многу поголем во однос на индивидуалните слушни амплификатори. Кога кохлеарниот имплант ќе се вгради во најрана возраст резултатите можат да доведат дури и до 100% активно вклучување на лицето во социјалната средина

RECEPTION AND AESTHETICS OF COMMUNICATION IN TEACHING MACEDONIAN LANGUAGE AND LITERATURE

Teaching Macedonian language and literature is an interesting field for study and didactics where various program fields merge – it teaches various topics from the fields of LANGUAGE, LITERATURE, DRAMA, FILM etc. The accent of our research is on interpreting literature and its positive impact on developing students’ personality. By applying the theory of reception of artistic contents and the method of literary and aesthetic communication in teaching interpretation of literature works, we made a research of the effects and possibilities of achieving educational and upbringing aims of tuition as well as developing emotional literacy of students

Gamification and blended learning in vocational training and coaching in short courses

Vocational training and coaching delivered through short courses and workshops, needs to be as effective as possible due to several reasons: learners (and their employers) invest their time and energy, they expect direct usefulness of the course content and roadmap on how to implement the knowledge into real-life problems, there is certain extent of professional maturity that expects proper balance of theoretical and practical aspects and the outcomes are evident in short time for the benefit of all, or for the worse. These reasons motivated the trainers to use a specific instructional design that embodies gamification, blended learning and coaching for vocational training in short courses for group of participants from Western Balkans countries, with diverse backgrounds, languages, professions, education, personal and collective goals on the topic of preparing successful project proposals for funding, supported by the Western Balkans Alumni Association projects. The specifics in this instructional design have been multifold, compared to traditional training and coaching. One of the novel aspects is the combination of trainers related to the course content of projects funding from various aspects - National Agency expertise, academic, governmental and non-governmental experience, project evaluation and business practitioners. This setting of training facilitated by representative of almost every stakeholder in the higher educational ecosystem and articulated through the curricula of the trainers is aimed to enable overall knowledge apprehension, networking and immediate feedback loops. The incorporation of virtual activities before, during and after the in-person course utilises blended learning mashup of various tools such as e-learning platform for asynchronous communication, social networks for synchronous communication, webinar tool for virtual presence, video tutorials for future reference and expanded dissemination and personal contact for coaching. Another novelty in this approach is in the gamification aspect - introducing scout-game in the forest, using broad range of symbolic matrices - of compasses, maps, planned activities and unplanned events, training of skills and situational awareness, progress mechanics, challenges to achieve teamwork towards outputs and outcomes. And last but not least, the balance of theoretical and practical aspects is achieved by inviting each participant to have own working example and apply the concepts while receiving immediate feedback, or working on collective example - for all of which, follow up coaching is provided. The ‘magic’ of effective project proposals is complemented with appropriate change management and tactical management. The cognitive and knowledge dimension categories and components have been addressed in their entirety through the extended Bloom taxonomy and the evaluation has been made in formative and summative manner. The learning experience with our instructional design in this pilot instance happens for each participant - on the side of the learners and on the side of the trainers and other HEI stakeholders, including the WBAA - with specific goal to enable emergent effects of networked learners that can put their knowledge, skills and competences in right direction and produce primary and secondary effects for the Western Balkans region and EU