Using exomarkers to assess mitochondrial reactive species in vivo

Background: The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. Scope of review: One approach towards achieving this goal is the use of exomarkers. In this, exogenous probe compounds are administered to the intact organism and are then transformed by the reactive molecules in vivo to produce a diagnostic exomarker. The exomarker and the precursor probe can be analysed ex vivo to infer the identity and amounts of the reactive species present in vivo. This is akin to the measurement of biomarkers produced by the interaction of reactive species with endogenous biomolecules. Major conclusions and general significance: Our laboratories have developed mitochondria-targeted probes that generate exomarkers that can be analysed ex vivo by mass spectrometry to assess levels of reactive species within mitochondria in vivo. We have used one of these compounds, MitoB, to infer the levels of mitochondrial hydrogen peroxide within flies and mice. Here we describe the development of MitoB and expand on this example to discuss how better probes and exomarkers can be developed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Abbreviations: EPR, electron paramagnetic resonance; GFP, green fluorescent protein; 4-HNE, 4-hydroxynonenal; MitoB, 3-(dihydroxyboronyl)benzyltriphenylphosphonium bromide; MitoP, (3-hydroxybenzyl)triphenylphosphonium bromide; ROS, reactive oxygen species; SOD, superoxide dismutase; TPMP, methyltriphenylphosphonium; TPP, triphenylphosphonium catio

Die polnische Freiheit und Preußens Friedrich : Oder: Über die Furcht der Hohenzollern vor dem polnischen Freiheitsbazillus

Aus Anlass des 300. Geburtstags von „Friedrich dem Großen“ im Jahr 2012 erinnert der Autor daran, dass der Preußenkönig nicht nur ein Philosoph und Aufklärer war, sondern auch ein Verächter von „polnischer Freiheit“ und dass er mit seiner Politik erheblich zur deutsch-polnischen Verfeindung mit beigetragen hat

Invader presence disrupts the stabilizing effect of species richness in plant community recovery after drought

Abstract Higher biodiversity can stabilize the productivity and functioning of grassland communities when subjected to extreme climatic events. The positive biodiversity–stability relationship emerges via increased resistance and/or recovery to these events. However, invader presence might disrupt this diversity–stability relationship by altering biotic interactions. Investigating such disruptions is important given that invasion by non‐native species and extreme climatic events are expected to increase in the future due to anthropogenic pressure. Here we present one of the first multisite invader × biodiversity × drought manipulation experiment to examine combined effects of biodiversity and invasion on drought resistance and recovery at three semi‐natural grassland sites across Europe. The stability of biomass production to an extreme drought manipulation (100% rainfall reduction; BE: 88 days, BG: 85 days, DE: 76 days) was quantified in field mesocosms with a richness gradient of 1, 3, and 6 species and three invasion treatments (no invader, Lupinus polyphyllus, Senecio inaequidens). Our results suggest that biodiversity stabilized community productivity by increasing the ability of native species to recover from extreme drought events. However, invader presence turned the positive and stabilizing effects of diversity on native species recovery into a neutral relationship. This effect was independent of the two invader's own capacity to recover from an extreme drought event. In summary, we found that invader presence may disrupt how native community interactions lead to stability of ecosystems in response to extreme climatic events. Consequently, the interaction of three global change drivers, climate extremes, diversity decline, and invasive species, may exacerbate their effects on ecosystem functioning

Fusion Techniques in Biomedical Information Retrieval

For difficult cases clinicians usually use their experience and also the information found in textbooks to determine a diagnosis. Computer tools can help them supply the relevant information now that much medical knowledge is available in digital form. A biomedical search system such as developed in the Khresmoi project (that this chapter partially reuses) has the goal to fulfil information needs of physicians. This chapter concentrates on information needs for medical cases that contain a large variety of data, from free text, structured data to images. Fusion techniques will be compared to combine the various information sources to supply cases similar to an example case given. This can supply physicians with answers to problems similar to the one they are analyzing and can help in diagnosis and treatment planning

CSF and Brain Structural Imaging Markers of the Alzheimer's Pathological Cascade

10.1371/journal.pone.0047406PLoS ONE712

Бринзоламид/тимолол и латанопрост в лечении псевдоэксфолиативной глаукомы: сравнительное исследование

PURPOSE: To compare the long-term effectiveness of pseudoexfoliative glaucoma (PEG) treatment with a fixed combination (FC) brinzolamide/timolol vs. latanoprost by a comprehensive assessment of structural and functional changes, as well as indicators of arterial ocular blood flow. METHODS: We observed 42 patients with PEG who received FC brinzolamide/timolol (22 patients) 2 times daily or latanoprost once a day (20 patients). The groups were homogeneous for age (66.05±1.241 in brinzolamide/ timolol group and 63.8±2.09 in latanoprost group, p=0.36) and glaucoma stages (MD -6.43±1.51 dB in brinzolamide/ timolol group and -8.02±2.08 dB in latanoprost group, p=0.54), intraocular pressure (IOP) levels were also comparable (19.59±0.79 mm Hg in brinzolamide/timolol group and 19.94±0.88 mm Hg in latanoprost group, p=0.77). The functional and morphometric parameters, studied by means of standard automated perimetry and spectral optical coherence tomography, and ocular blood flow parameters, measured by color Doppler Imaging with impulse Doppler sonography, were subjected to a comparative evaluation. Follow up period was 10.5±0.363 month. RESULTS: A significant IOP reduction, compared with baseline was observed in both groups: 11% from baseline in brinzolamide/timolol group (p=0.005) and 12.5% from baseline in latanoprost group (p=0.011). MD was improved in brinzolamide/timolol group: by 1.2±0.37 dB (p=0.003). No statistically significant difference in RNFL, GlV and GCC was obtained in both groups during the follow up period. However, by the end of 12 months a significant increase of FLV was noted in latanoprost group (p=0.04). By the end of the observation period patients treated with brinzol-amide/timolol showed an increase in diastolic blood flow in the ophthalmic artery (p=0.044) and systolic blood flow in the lateral posterior short ciliary artery (p=0.011). CONCLUSION: FC brinzolamide/timolol and latanoprost demonstrate a significant hypotensive efficacy in PEG, however FC brinzolamide/timolol unlike latanoprost provides stabilization of glaucomatous optic neuropathy, as evidenced by the preservation of visual function and morpho-metric parameters of the retina and optic nerve, as well as an improved arterial ocular blood flow.ЦЕЛЬ. Сравнить долгосрочную эффективность лечения псевдоэксфолиативной глаукомы (ПЭГ) фиксированной комбинацией бринзоламид/тимолол (ФК бринзоламид/ тимолол) с латанопростом на основании комплексной оценки структурных и функциональных изменений, а также показателей артериального глазного кровотока. МЕТОДЫ. В исследовании приняли участие 42 пациента с ПЭГ, получавшие ФК бринзоламид/тимолол (22 больных) 2 раза в день или латанопрост 1 раз в день (20 больных). Группы были однородны по возрасту (66,05±1,24 года в группе, получавшей ФК бринзоламид/тимолол, и 63,8±2,09 года в группе, получавшей латанопрост, р=0,36), по стадиям глаукомы (MD -6,43±1,51 дБ в группе ФК бринзоламид/тимолол и -8,027±2,08 дБ в группе латанопрост, р=0,54), а также по исходному уровню внутриглазного давления (19,59±0,79 и 19,94±0,88 мм рт.ст. соответственно в группах ФК бринзоламид/тимолол и латанопрост, р=0,77). Сравнительной оценке подвергнуты функциональные и морфометрические показатели, полученные при стандартной автоматизированной периметрии и спектральной оптической когерентной томографии, а также параметры регионарной гемодинамики глаза, измеренные в динамике методом цветового доп-плеровского картирования с импульсной допплерогра-фией. Средний срок наблюдения составил 10,5±0,36 мес. РЕЗУЛЬТАТЫ. В обеих группах больных наблюдалось достоверное по сравнению с исходным снижение ВГД, которое составило в группе ФК бринзоламид/тимолол 11% от исходного (p=0,005) и в группе латанопрост 12,5% от исходного (p=0,011). Было отмечено улучшение периметрического индекса MD у больных, получавших ФК бринзоламид/тимолол, на 1,2±0,37 дБ по сравнению с исходным (p=0,003). Статистически значимого изменения морфометрических показателей в динамике не было отмечено ни в одной группе, за исключением достоверного увеличения индекса FLV (p=0,04) у больных, получавших латанопрост. У пациентов, лечившихся ФК бринзоламид/тимолол, к концу наблюдения отмечено увеличение диастолической скорости кровотока в глазной артерии (p=0,044) и систолической скорости кровотока в латеральной задней короткой цилиарной артерии (p=0,011). ЗАКЛЮЧЕНИЕ. ФК бринзоламид/тимолол и латанопрост обладают выраженной гипотензивной эффективностью в лечении ПЭГ, однако ФК бринзоламид/тимолол, но не латанопрост, обеспечивает стабилизацию глаукомной оптической нейропатии, о чем свидетельствует сохранение зрительных функций и морфометрических характеристик сетчатки и зрительного нерва, а также улучшение артериального глазного кровотока

P1‐349: Advancing Clinical And Biomarker Research In Ad: The Lead Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152716/1/alzjjalz201906904.pd

The importance of service quality in British Muslim’s choice of an Islamic or non-Islamic bank account

Using an extended SERVQUAL model, this study identifies and compares the importance of service quality to Muslim consumers with an Islamic or non-Islamic bank account in a non-Muslim country, Britain. Eight group discussions and survey with 300 Muslims were conducted. Five dimensions of service quality were identified, i.e. Responsiveness, Credibility, Islamic Tangibles, Accessibility and Reputation. These differ in structure and content from the original SERVQUAL developed in the west and the subsequent CARTER model constructed in a Muslim country. In addition, significant differences were found in the importance rating of items by respondents holding an account with an Islamic bank compared to those with a non-Islamic bank account. This study is one of the first to identify and compare the importance of service quality between Islamic and non-Islamic bank account holders in a western non-Muslim country. The results advance our understanding of the impact of culture on SERVQUAL. The study provides insight into Muslims’ bank choice and helps bank managers of both Islamic and non-Islamic banks to focus their attention on the service quality dimensions that matter most to Muslim customers