CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance

Cytotoxic T lymphocyte antigen-4 (CTLA-4) plays a critical role in negatively regulating T cell responses and has also been implicated in the development and function of natural FOXP3+ regulatory T cells. CTLA-4–deficient mice develop fatal, early onset lymphoproliferative disease. However, chimeric mice containing both CTLA-4–deficient and –sufficient bone marrow (BM)–derived cells do not develop disease, indicating that CTLA-4 can act in trans to maintain T cell self-tolerance. Using genetically mixed blastocyst and BM chimaeras as well as in vivo T cell transfer systems, we demonstrate that in vivo regulation of Ctla4−/− T cells in trans by CTLA-4–sufficient T cells is a reversible process that requires the persistent presence of FOXP3+ regulatory T cells with a diverse TCR repertoire. Based on gene expression studies, the regulatory T cells do not appear to act directly on T cells, suggesting they may instead modulate the stimulatory activities of antigen-presenting cells. These results demonstrate that CTLA-4 is absolutely required for FOXP3+ regulatory T cell function in vivo

Analysis of arterial intimal hyperplasia: review and hypothesis

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Despite a prodigious investment of funds, we cannot treat or prevent arteriosclerosis and restenosis, particularly its major pathology, arterial intimal hyperplasia. A cornerstone question lies behind all approaches to the disease: what causes the pathology? Hypothesis: I argue that the question itself is misplaced because it implies that intimal hyperplasia is a novel pathological phenomenon caused by new mechanisms. A simple inquiry into arterial morphology shows the opposite is true. The normal multi-layer cellular organization of the tunica intima is identical to that of diseased hyperplasia; it is the standard arterial system design in all placentals at least as large as rabbits, including humans. Formed initially as one-layer endothelium lining, this phenotype can either be maintained or differentiate into a normal multi-layer cellular lining, so striking in its resemblance to diseased hyperplasia that we have to name it "benign intimal hyperplasia". However, normal or "benign " intimal hyperplasia, although microscopically identical to pathology, is a controllable phenotype that rarely compromises blood supply. It is remarkable that each human heart has coronary arteries in which a single-layer endothelium differentiates earl

Mechanism of cellular rejection in transplantation

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

Muscle pain induced by hypertonic saline in the knee extensors decreases single-limb isometric time to task failure

Purpose: Increased nociceptive activity and the experience of exercise-induced pain (EIP) may contribute to fatigue during endurance exercise. To investigate this, a pain model that produces pain similar to EIP and decouples its’ relationship to exercise intensity is required. This study 1) compared the quality of pain caused by a hypertonic saline injection into the vastus lateralis in resting and exercise conditions, and 2) investigated whether this pain contributes to changes in time to task failure. Methods: On separate days, eighteen participants completed a time to task failure at 20% maximal voluntary torque (MVT), a resting hypertonic saline intramuscular injection, and in a further three visits a time to task failure at 10% MVT following injection of isotonic saline, hypertonic saline or a control (no injection). Results: In a subset of eligible participants (n = 12), the hypertonic saline combined with 10% MVT produced a qualitative experience of pain (assessed by the McGill Pain Questionnaire) that felt similar to EIP. 10% MVT with hypertonic saline significantly elevated pain intensity in the first 20% of the time to task failure and caused a significantly (P < 0.05) shorter time to task failure (448 ± 240 s) compared with the isotonic saline (605 ± 285 s) and control (514 ± 197 s) conditions. Conclusion: These findings demonstrate that hypertonic saline increases the intensity of pain during exercise, which results in a faster occurrence of exercise-induced fatigue. These results provide important evidence supporting pain as a limiting factor in endurance performance

Імідж компаній: маркетингові і фінансові комунікації

Основною метою дослідження є оцінка якості економічних та фінансових даних з точки зору задоволення вимог акціонерів, а також впливу, який структура акцій може мати на економічну та фінансову інформаційну систему компанії. Підставами для теоретичної підготовки були систематичний огляд та критичний аналіз літератури з області дослідження. Згідно з результатами дослідження літератури, були розроблені зв'язки між областями дослідження та гіпотезою взаємозв'язку між статусом держави, як зацікавленої сторони, та якістю інформації, яка була опублікована в щорічних звітах. Аналізована вибірка спочатку складалася з тих компаній (105), які були зареєстровані на фондовій біржі Бухареста, тоді як метод оцінки якості розкриття інформації базувався на методі скорингу, тобто на балах, що надаються класифікованим елементам, характер простих або похідних показників. Після застосування критеріїв включення і виключення залишилося лише 65 компаній. Об'єктом дослідження є компанії, які готують свої фінансові звіти з використанням МСФЗ (Міжнародні стандарти фінансової звітності). Основним джерелом інформації були щорічні або проміжні опубліковані фінансові звіти. Ця стаття показує, що економічні та фінансові комунікації повинні покращувати інформаційну прозорість, що є ключовим елементом для підвищення достовірності. Навіть якщо практичні приклади дослідження зосереджені лише на вимогах зацікавлених сторін, якість економічного та фінансового розкриття вимагає, щоб надана інформація мала всі ті особливості, які характеризують високоякісну інформацію, тобто вона повинна бути актуальною та точною, легко зрозумілою, своєчасною, порівняною і перевіреною. Важливість цього дослідження випливає з того факту, що одержувачі фінансової інформації стають все більш і більш зацікавленими в якості останньої, характеристиці, яка по суті є основою їх рішень стосовно суб'єкта господарювання, що звітує. Результати дослідження можуть бути корисними для зацікавлених сторін, бізнессередовища, фінансово-банківських установ, держави, підкреслюючи важливість, потребу та переваги якісної економічної та фінансової комунікації в процесі прийняття рішень.The main purpose of the study is to evaluate the quality of the economic and financial data from the point of view of satisfying the shareholders’ demands as well as of the influences that the structure of the shareholding can have on a company’s economic and financial informational system. The bases for the theoretical background were a systematic overview and a critical analysis of the literature from the study field. According to the findings from the literature study, links were developed between the study areas and a hypothesis of the relationship between the state’s status as a stakeholder and the quality of the information that was published in the annual reports. The analysed sample initially was made up of those companies (105) that were listed on the Stock Market of Bucharest whereas the evaluation method of the quality of disclosure was based on the scoring method, i.e. the scoring points that are given to the classified elements, the nature of the simple or derivative indicators. After applying the inclusion and exclusion criteria remained only 65 of the company. The object of research is the companies that prepare their financial reports using the IFRS reference (International Financial Reporting Standards). The main information sources were the annual or interim published financial reports. This paper shows that economic and financial communication needs to make improvements in terms of the informational transparency that is a key element for building up its credibility. Even if the study’s practical examples focussed only on the stakeholders’ demands, the quality of the economic and financial disclosure requires that the supplied information has all those features that characterize high-quality information, that is the must be relevant and precise, easy to understand, timely, comparable and verifiable. The importance of the present study results from the fact that the beneficiaries of financial information are becoming more and more interested in quality information, a characteristic that is basically the foundation of their decisions in regards to the reporting entity. The results of the study may be useful to the stakeholders, the business environment, the financial-banking institutions, the state, highlighting the importance, need and benefits of a qualitative economic and financial communication in the decision-making process