2,757 research outputs found
Understanding diabetic retinopathy
No full textA recent survey shows that diabetes affect 92.4 million people in mainland China [1], among which 16.9 million have diabetic retinopathy (DR) [2]. DR is one of the major causes of blindness in the working age population in both developing and developed countries. Although the exact mechanism by which diabetes causes retinopathy remains elusive, several hypotheses have been postulated to explain pathogenies of the disease. Here we invited five groups of scientists and clinicians to share their recent discoveries and expert opinions in molecular biology, pathophysiology, genetics, and epigenetics of DR.SCI(E)PubMed中国科学引文数据库(CSCD)EDITORIAL [email protected]
A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation
No full textPervasive neuroinflammation occurs in many neurodegenerative diseases, including Alzheimer’s disease (AD). SPI1/PU.1 is a transcription factor located at a genome-wide significant AD-risk locus and its reduced expression is associated with delayed onset of AD. We analyzed single-cell transcriptomic datasets from microglia of human AD patients and found an enrichment of PU.1-binding motifs in the differentially expressed genes. In hippocampal tissues from transgenic mice with neurodegeneration, we found vastly increased genomic PU.1 binding. We then screened for PU.1 inhibitors using a PU.1 reporter cell line and discovered A11, a molecule with anti-inflammatory efficacy and nanomolar potency. A11 regulated genes putatively by recruiting a repressive complex containing MECP2, HDAC1, SIN3A, and DNMT3A to PU.1 motifs, thus representing a novel mechanism and class of molecules. In mouse models of AD, A11 ameliorated neuroinflammation, loss of neuronal integrity, AD pathology, and improved cognitive performance. This study uncovers a novel class of anti-inflammatory molecules with therapeutic potential for neurodegenerative disorders
Automating the determination of wave speed using the pu-loop method
No full textThe PU-loop (pressure-velocity loop) is a method for determining wave speed and relies on the linear relationship between the pressure and velocity in the absence of reflected waves. This linearity of the PU-loop during early systole, which is directly related to wave speed, has always been established by eye. This paper presents a new technique that establishes this linearity and thus determining wave speed online. Pressure and flow were measured in the ascending aorta of 11 anesthetised dogs. The slope of the PU-loop, indicating wave speed was determined by eye and by using the new technique. The difference between the slopes of the two methods is in the order of 3%. The new technique is convenient and allows for the online assessment of wave speed, which could be used as a bedside tool for the assessment of arterial compliance
Visual response properties of retinal ganglion cells in the royal college of surgeons dystrophic rat
No full textPURPOSE. Alterations in retinal ganglion cell response patterns were profiled in dystrophic Royal College of Surgeons ( hereafter RCS) rats over the first 100 postnatal days as a baseline for retinal rescue and vision restoration strategies. This method enabled the evaluation of the extent to which postreceptoral neuronal attributes in degenerating retinas mirror inferred declines in photoreceptor function. METHODS. Single-unit responses from large retinal ganglion cells were recorded from age-matched dystrophic RCS (RCS-rdy(-)) and congenic RCS-p(+) ( hereafter wild-type or wt) rats were recorded in vitro under visual control. Cells were profiled with conventional spatial and flux stimulus modulations. RESULTS. Ganglion cell single unit and population attributes alter slowly over the course of photoreceptor degeneration in dystrophic RCS rats, with significant decreases in apparent receptive field size, contrast sensitivity, and threshold sensitivity detected by the first month of life. Spatial frequency tuning and contrast responses were extremely weak by postnatal day ( P) 76, paralleled by a progressive decline in signal-to-noise (S-N) ratio to roughly unity by postnatal day (P) 107. This decline was only a simple loss of responsivity, as background firing rates increased substantially over time. Whereas wt retinas were dominated by ON-center cells (15/23 cells), dystrophic animals were dominated by OFF-center cells by P47 (24/27 cells). CONCLUSIONS. The first definitive signs of degeneration in dystrophic RCS rats are parallel decreases in ganglion cell threshold sensitivity and receptive field size, followed by deterioration in spatial summation. Arguably, these changes can be qualitatively explained as photoreceptor signaling losses. However, the apparent shift in population profile from ON- to OFF-center ganglion cells long before loss of the b-wave at P90 implies that a reactive mechanism such as bipolar cell rewiring and/or transformation of neuronal phenotypes occur during the early phase of photoreceptor stress, before rod and cone death.OphthalmologySCI(E)PubMed32ARTICLE83579-35854
A pu -k lativusrag fejleményei a déli szamojédban
No full textIn the light of newly published material, the author investigates various Selkup and Kamassian suffixes containing the developments of PU -K and gives her reasons why she does interpret them as continuations of the PU lative suffix
KELVIN-HELMHOLTZ INSTABILITY IN COLLISIONLESS SPACE PLASMAS
No full textPhysics, Fluids & PlasmasSCI(E)9ARTICLE2440-447
Literacy and the vernacular : a case study based on the post-colonial history of Mauritius, with particular reference to Mauritian Creole
No full textThis thesis examines the process of the literization of the vernacular, and seeks to establish the island of Mauritius as a case study of this process. The concept of literization equates standardization of the vernacular with its use as a written language. Four issues are established as central to this process: ideological, educational, sociocultural and technical.
The thesis investigates the particular sociolinguistic situation of Mauritius, and examines each of these issues in relation to Mauritian Creole. It demonstrates the role that Mauritian Creole plays in Mauritian society, and how, since independence, issues relating to ideology, education, and the cultural and technical aspects of standardization, have been involved in the promotion of the language. The interaction between these issues is apparent throughout the thesis, and manifested in the work of Ledikasyon pu Travayer (LPT), the only organization in Mauritius to provide literacy tuition in Mauritian Creole. The thesis seeks to show that their unified approach to literacy, standardization, and the promotion of Mauritian Creole exemplifies the issues involved, and provides the best basis for the establishment of Mauritian Creole as a standard language.
The analysis of the situation in Mauritius within the framework of wider issues of the literization of the vernacular permits a comparison to other former colonies facing problems of language choice, and places these issues within the wider sociolinguistic context of standardization
Molecular size distribution of Pu in the presence of humic substances in river and groundwaters
No full textThe association properties of Pu with aquatic humic substances in a 0.01M NaClO4 solution at pH 6–8 were studied on the basis of molecular size distribution. Seven humic substances were isolated from river water and groundwaters using XAD extraction technique. They were used for comparing their effects on the association of Pu. In the presence of humic acid, the dominant molecular size of Pu was 100–30 kDa. In the presence of fulvic acid, Pu exhibited three dominant molecular sizes: 30–10 kDa, 30–5 kDa, and less than 5 kDa. The association of Pu-humus complexes might be controlled by the molecular size distribution of humic substances and characteristics of their respective size fractions
Electron Elastic Collisions with Pu, Am and Lr Actinide Atoms
No full textSynopsis The robust Regge-pole methodology which embeds the crucial electron correlations and the vital core-polarization interaction is used to explore negative-ion formation in the actinide atoms Pu, Am and Lr through the electron elastic total cross sections (TCSs) calculation. The TCSs are found to be characterized by ground, metastable and excited anionic formation, whence we extract the anionic binding energies and compare them with existing electron affinities. The TCSs exhibit both atomic and molecular behavior in addition to polar- ization-induced metastable TCSs
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