Identification of an Amino-Terminal Fragment of Apolipoprotein E4 that Localizes to Neurofibrillary Tangles of the Alzheimer’s Disease Brain

Although the risk factor for harboring the apolipoprotein E4 (apoE4) allele in late-onset Alzheimer’s disease (AD) is well known, the mechanism by which apoE4 contributes to AD pathogenesis has yet to be clarified. Preferential cleavage of the ApoE4 isoform relative to other polymorphic forms appears to be significant, as the resulting fragments are associated with hallmarks of AD. To examine the possible role of apoE4 proteolysis in AD, we designed a site-directed antibody directed at position D172, which would yield a predicted amino-terminal fragment previously identified in AD brain extracts. Western blot analysis utilizing this novel antibody, termed the amino-terminal apoE4 cleavage fragment (nApoE4CF) Ab consistently identified the predicted amino-terminal fragment (~18 kDa) in several commercially available forms of human recombinant apoE4 purified from E. coli. Mass spectrometry confirmed the identity of this 18 kDa fragment as being an amino-terminal fragment of apoE4. Immunohistochemical experiments indicated the nApoE4CF Ab specifically labeled neurofibrillary tangles (NFTs) in AD frontal cortex sections that colocalized with the mature tangle marker PHF-1. Taken together, these results suggest a novel cleavage event of apoE4, generating an amino-terminal fragment that localizes within NFTs of the AD brain

Pharmacokinetic study on pradofloxacin in the dog – Comparison of serum analysis, ultrafiltration and tissue sampling after oral administration

Background: Pradofloxacin, a newly developed 8-cyano-fluoroquinolone, show enhanced activity against Grampositive organisms and anaerobes to treat canine and feline bacterial infections. The purpose of this cross-over study was to measure the unbound drug concentration of pradofloxacin in the interstitial fluid (ISF) using ultrafiltration and to compare the kinetics of pradofloxacin in serum, ISF and tissue using enrofloxacin as reference. Results: After oral administration of enrofloxacin (5 mg/kg) and pradofloxacin (3 mg/kg and 6 mg/kg, respectively), serum collection and ultrafiltration in regular intervals over a period of 24 h were performed, followed by tissue sampling at the end of the third dosing protocol (pradofloxacin 6 mg/kg). Peak concentrations of pradofloxacin (3 mg/kg) were 1.55±0.31 μg/ml in the ISF and 1.85±0.23 μg/ml in serum and for pradofloxacin (6 mg/kg) 2.71±0.81 μg/kg in the ISF and 2.77±0.64 μg/kg in serum; both without a statistical difference between ISF and serum. Comparison between all sampling approaches showed no consistent pattern of statistical differences. Conclusions: Despite some technical shortcomings the ultrafiltration approach appears to be the most sensitive sampling technique to estimate pharmacokinetic values of pradofloxacin at the infection site. Pharmacokinetics – Pradofloxacin – Ultrafiltration – Dog – Oral Administration

Brands in international and multi‐platform expansion strategies: economic and management issues

Powerful media branding has historically facilitated successful international expansion on the part of magazine and other content forms including film and TV formats. Multi-platform expansion is now increasingly central to the strategies of media companies and, as this chapter argues, effective use of branding in order to engage audiences effectively and to secure a prominent presence across digital platforms forms a core part of this. Drawing on original research into the experience of UK media companies, this chapter highlights some of the key economic, management and socio-cultural issues raised by the ever-increasing role of brands and branding in the strategies of international and multi-platform expansion that are increasingly common- place across media

THE LONG TRAIL: A CHIMERA-LIKE FOSSIL CRUSTACEAN INTERPRETED AS DECAPODA, STOMATOPODA, AMPHIPODA AND FINALLY ISOPODA

The process of interpreting and evaluating a fossil is a difficult task. Isopoda is a species rich group of peracarid eumalacostracans which represent quite a challenge when found as fossils, independent of whether we are working with fragmentary or more complete specimens. Here we describe a new fossil species of crustacean, Platuropodus odysseus n. gen. n. sp., from the Irati Formation, Permian of Paraná Basin, Brazil. After misinterpretations, the fossil taxon is recognised here as a representative of Isopoda. The new species presents characters found in Phreatoicidea, Asellota and Oniscidea in a unique combination for the fossil and extant record, such as two pairs of sub-chelate anterior trunk appendages, a short region after the anus and flat uropods. This chimera-like morphology and a morphometric analysis of the sub-chelae indicate convergent evolution in the early diversification of Isopoda. The morphological diversification present in the Palaeozoic and Mesozoic fossil record of Eumalacostraca indicate a “push of the past” effect in different ingroups of Peracarida

A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals

Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli, suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus. Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level

Lagrangian Reachabililty

We introduce LRT, a new Lagrangian-based ReachTube computation algorithm that conservatively approximates the set of reachable states of a nonlinear dynamical system. LRT makes use of the Cauchy-Green stretching factor (SF), which is derived from an over-approximation of the gradient of the solution flows. The SF measures the discrepancy between two states propagated by the system solution from two initial states lying in a well-defined region, thereby allowing LRT to compute a reachtube with a ball-overestimate in a metric where the computed enclosure is as tight as possible. To evaluate its performance, we implemented a prototype of LRT in C++/Matlab, and ran it on a set of well-established benchmarks. Our results show that LRT compares very favorably with respect to the CAPD and Flow* tools.Comment: Accepted to CAV 201

Positive Semidefiniteness and Positive Definiteness of a Linear Parametric Interval Matrix

We consider a symmetric matrix, the entries of which depend linearly on some parameters. The domains of the parameters are compact real intervals. We investigate the problem of checking whether for each (or some) setting of the parameters, the matrix is positive definite (or positive semidefinite). We state a characterization in the form of equivalent conditions, and also propose some computationally cheap sufficient\,/\,necessary conditions. Our results extend the classical results on positive (semi-)definiteness of interval matrices. They may be useful for checking convexity or non-convexity in global optimization methods based on branch and bound framework and using interval techniques

Principles of interdisciplinary integration of research work of dental students as a condition of improvement of quality of preparation of graduates

Тhe analysis and the principles of interdisciplinary integration of research work of students-dentists. Defined: the principles of MI are the structural basis of creative development of personality of students – the main condition of improvement of quality of preparation of graduates of dental.Проведен анализ и определены принципы междисциплинарной интеграции научно-исследовательской работы студентов-стоматологов. Определено: принципы МИ являются структурной основой творческого развития личности студентов — главным условием повышения качества подготовки выпускников-стоматологов

Role of the motivating factor in obtaining a profession

The profession of a dentist covers a pretty broad spectrum of activities: treatment, prevention, surgery, prosthetics, bite correction and more. The physician must possess a diagnostic mindset, be able to use modern equipment, have the skills of the art modeling to constantly improve your own skills and learn the latest treatments or prosthetics. In the article using the designed questionnaire, the authors determine leading factors influencing the professional choice of the child.Профессия стоматолога охватывает довольно обширный спектр деятельности: лечение, профилактика, хирургические вмешательства, протезирование, исправление прикуса и многое другое. Врач должен обладать диагностическим мышлением, уметь пользоваться современной аппаратурой, владеть навыками художественного моделирования, постоянно повышать собственную квалификацию и осваивать самые новейшие методы лечения или протезирования. В статье с помощью разработанной анкеты авторы определяют лидирующие факторы, влияющие на профессиональный выбор ребенка

Coaching technologies in the educational process at the department of therapeutic dentistry: innovations conservative periodontics

Тhe article discusses the need for new innovative educational technologies to improve learning and realizing the potential of dental students; coaching technologies to enhance the efficiency of interaction in the education system among students-dentists and teachers. It is shown that the technology of coaching in the educational process at the Department of operative dentistry at present are promising and useful and allows the release of USMU is conducted of specialists with not only theoretical but also practical training.В статье рассматривается необходимость поиска новых инновационных образовательных технологий для совершенствования процесса обучения и раскрытия потенциала студентов-стоматологов; технологии коучинга для повышения эффективности взаимодействия в системе образования между старшекурсниками-стоматологами и преподавателем. Показано, что технологии коучинга в учебном процессе на кафедре терапевтической стоматологии в настоящее время являются перспективными и полезными и позволяют выпустить из УГМУ специалистов, имеющих не только теоретическую, но и практическую подготовку