Oxidative stress, advanced glycation end products and residual renal function in the rat model of unilateral ureteral obstruction: effects of phlogenzym and losartan

Aim. Oxidative stress plays a role in the pathogenesis of ureteral obstruction. Methods. We studied parameters of oxidative status, levels of advanced glycation end products (AGEs), and contralateral (CL) kidney function in the rat model of unilateral ureteral obstruction (UUO). The effect of Phlogenzym (12 mg/day orally); losartan (20 mg/l in drinking water), and their combination was studied. Results. In placebo-administered UUO rats AGEs and malondialdehyde levels were higher than in the sham operated controls. Function of the CL kidney was slightly impaired, its collagen content and protein/deoxyribonucleic acid ratio (P/DNA) in the glomeruli increased. All treatments prevented the rise in collagen content, P/DNA ratio, and improved CL kidney function. Phlogenzym ameliorated lipid peroxidation and AGE levels. Conclusions. In the model of UUO systemically increased oxidative stress may play a role in development of tubulointerstitial fibrosis and in the functional impairment of the CL kidney. Suppression of the oxidative stress and blockade of angiotensin-1 receptors might mitigate the progression of obstructive uropathy.Оксидативний стрес відіграє значну роль у патогенезі обструкції сечоводу. Мета роботи полягала у вивченні параметрів оксидативного статусу, оцінюванні рівня кінцевих продуктів глікації і функціонування контралатеральної нирки на моделі щурів з унілатеральною обструкцією сечоводу (УОС). Методи. На моделі УОС досліджували ефекти флогензиму (12 мг в день орально) і лосартану (20 мг/л у питній воді), а також їхньої комбінації. Результати. У щурів з УОС, які отримували плацебо, рівень накопичення кінцевих продуктів глікації та малондіальдегіду виявився вищим, ніж у несправжньооперованих контрольних щурів. Функціонування контралатеральної нирки незначно погіршилося, концентрація колагену і співвідношення вмісту білок/дезоксирибонуклеїнова кислота (P/ DNA) у клубочку нирки підвищені. Обробка досліджуваними лікарськими засобами запобігала збільшенню вмісту колагену, зростанню показника співвідношення P/DNA та покращувала функціонування колатеральної нирки. Флогензим сприяв підвищенню рівня перекисного окиснення ліпідів та кінцевих продуктів глікації. Висновки. У моделі УОС систематичне збільшення оксидативного стресу може відігравати важливу роль у розвитку тубулоінтерстиційного фіброзу і порушенні функціонування контралатеральної нирки. Супресія оксидативного стресу та блокування рецептора ангіотензину-1 можуть послаблювати прогресію обструктивної уропатії.Оксидативный стресс играет значительную роль в патогенезе обструкции мочеточника. Цель работы состояла в изучении параметров оксидативного статуса, оценке уровня конечных продуктов гликации и функционирования контралатеральной почки на модели крыс с унилатеральной обструкцией мочеточника (УОМ). Методи. На модели УОМ исследовали эффекты флогензима (12 мг в день орально) и лосартана (20 мг/л в питьевой воде), а также их комбинации. Результаты. У крыс с УОМ, получавших плацебо, уровень конечных продуктов гликации и малондиальдегида оказался выше, чем у ложноооперованных контрольных крыс. Функционирование контралатеральной почки незначительно ухудшилось, концентрация коллагена и соотношение содержания белок/дезоксирибонуклеиновая кислота (P/DNA) в клубочке почки повысились. Обработка исследуемыми лекарственными средставами предотвращала увеличение содержания коллагена, показателя соотношения P/DNA и улучшала функционирование колатеральной почки. Флогензим способствовал возрастанию уровня перекисного окисления липидов и конечных продуктов гликации. Выводы. В модели УОМ систематическое увеличение оксидативного стресса может быть причиной развития тубулоинтерстиционного фиброза и нарушения функционирования контралатеральной почки. Супрессия оксидативного стресса и блокирование рецептора ангиотензина-1 можгут ослаблять прогрессию обструктивной уропатии

Surface-Enhanced Nitrate Photolysis on Ice

Heterogeneous nitrates photolysis is the trigger for many chemical processes occurring in the polar boundary layer and is widely believed to occur in a quasi-liquid layer (QLL) at the surface of ice. The dipole forbidden character of the electronic transition relevant to boundary layer atmospheric chemistry and the small photolysis/photoproducts quantum yields in ice (and in water) may confer a significant enhancement and interfacial specificity to this important photochemical reaction at the surface of ice. Using amorphous solid water films at cryogenic temperatures as models for the disordered interstitial air/ice interface within the snowpack suppresses the diffusive uptake kinetics thereby prolonging the residence time of nitrate anions at the surface of ice. This approach allows their slow heterogeneous photolysis kinetics to be studied providing the first direct evidence that nitrates adsorbed onto the first molecular layer at the surface of ice are photolyzed more effectively than those dissolved within the bulk. Vibrational spectroscopy allows the ~3-fold enhancement in photolysis rates to be correlated with the nitrates’ distorted intramolecular geometry thereby hinting at the role played by the greater chemical heterogeneity in their solvation environment at the surface of ice than in the bulk. A simple 1D kinetic model suggests 1-that a 3(6)-fold enhancement in photolysis rate for nitrates adsorbed onto the ice surface could increase the photochemical NO[subscript 2] emissions from a 5(8) nm thick photochemically active interfacial layer by 30%(60)%, and 2-that 25%(40%) of the NO[subscript 2] photochemical emissions to the snowpack interstitial air are released from the top-most molecularly thin surface layer on ice. These findings may provide a new paradigm for heterogeneous (photo)chemistry at temperatures below those required for a QLL to form at the ice surface

Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted1. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization. We defined around two dozen projection neuron types in the MOp-ul and derived an input-output wiring diagram, which will facilitate future analyses of motor control circuitry across molecular, cellular and system levels. This work provides a roadmap towards a comprehensive cellular-resolution description of mammalian brain architecture

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Leptin Levels Are Negatively Correlated with 2-Arachidonoylglycerol in the Cerebrospinal Fluid of Patients with Osteoarthritis. Leptin Levels Are Negatively Correlated with 2-Arachidonoylglycerol in the Cerebrospinal Fluid of Patients with Osteoarthritis

Abstract Backgroun

Photoformation of hydroxyl radical on snow grains at Summit, Greenland

We measured the photoformation of hydroxyl radical (OH) on snow grains at Summit, Greenland during the spring and summer. Midday rates of OH formation in the snow phase in the summer range from 130 to , expressed relative to the liquid equivalent volume of snow. Calculated formation rates of snow-grain OH based on the photolysis of hydrogen peroxide and nitrate agree well with our measured rates during summer, indicating that there are probably not other major sources of OH under these conditions. Throughout both the spring and summer, HOOH is by far the dominant source of snow-grain OH; on average, HOOH produces approximately 100 times more OH than does . Rates of OH photoformation have a strong seasonal dependence and increase by approximately a factor of 10 between early spring and summer at midday. The rate of OH photoformation on snow grains decreases rapidly with depth in the snowpack, with approximately 90% of photoformation occurring within the top 10 cm, although OH formation occurs to depths below 20 cm. The formation of OH on snow grains likely initiates a suite of reactions in the snowpack, including the transformation of organic carbon (OC) and oxidation of halides. The reaction of OH with OC probably forms a number of volatile organic compounds (VOCs) that are potentially emitted into the atmospheric boundary layer. Indeed, our measured rates of OH photoformation on snow grains are large enough that they could account for previously reported fluxes of VOCs from the snowpack at Summit, although the relative importance of thermal desorption and photochemical production for most of these VOCs still needs to be determined