232 research outputs found

    Near-infrared sensitivity enhancement of photorefractive polymer composites by pre-illumination

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    Among the various applications for reversible holographic storage media, a particularly interesting one is time-gated holographic imaging (TGHI). This technique could provide a noninvasive medical diagnosis tool, related to optical coherence tomography. In this technique, biological samples are illuminated within their transparency windowwith near-infrared light, and information about subsurface features is obtained by a detection method that distinguishes between reflected photons originating from a certain depth and those scattered from various depths. Such an application requires reversible holographic storage media with very high sensitivity in the near-infrared. Photorefractive materials, in particular certain amorphous organic systems, are in principle promising candidate media, but their sensitivity has so far been too low, mainly owing to their long response times in the near-infrared. Here we introduce an organic photorefractive material—a composite based on the poly(arylene vinylene) copolymer TPD-PPV—that exhibits favourable near-infrared characteristics. We show that pre-illumination of this material at a shorter wavelength before holographic recording improves the response time by a factor of 40. This process was found to be reversible. We demonstrate multiple holographic recording with this technique at video rate under practical conditions

    A High Incidence of Meiotic Silencing of Unsynapsed Chromatin Is Not Associated with Substantial Pachytene Loss in Heterozygous Male Mice Carrying Multiple Simple Robertsonian Translocations

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    Meiosis is a complex type of cell division that involves homologous chromosome pairing, synapsis, recombination, and segregation. When any of these processes is altered, cellular checkpoints arrest meiosis progression and induce cell elimination. Meiotic impairment is particularly frequent in organisms bearing chromosomal translocations. When chromosomal translocations appear in heterozygosis, the chromosomes involved may not correctly complete synapsis, recombination, and/or segregation, thus promoting the activation of checkpoints that lead to the death of the meiocytes. In mammals and other organisms, the unsynapsed chromosomal regions are subject to a process called meiotic silencing of unsynapsed chromatin (MSUC). Different degrees of asynapsis could contribute to disturb the normal loading of MSUC proteins, interfering with autosome and sex chromosome gene expression and triggering a massive pachytene cell death. We report that in mice that are heterozygous for eight multiple simple Robertsonian translocations, most pachytene spermatocytes bear trivalents with unsynapsed regions that incorporate, in a stage-dependent manner, proteins involved in MSUC (e.g., γH2AX, ATR, ubiquitinated-H2A, SUMO-1, and XMR). These spermatocytes have a correct MSUC response and are not eliminated during pachytene and most of them proceed into diplotene. However, we found a high incidence of apoptotic spermatocytes at the metaphase stage. These results suggest that in Robertsonian heterozygous mice synapsis defects on most pachytene cells do not trigger a prophase-I checkpoint. Instead, meiotic impairment seems to mainly rely on the action of a checkpoint acting at the metaphase stage. We propose that a low stringency of the pachytene checkpoint could help to increase the chances that spermatocytes with synaptic defects will complete meiotic divisions and differentiate into viable gametes. This scenario, despite a reduction of fertility, allows the spreading of Robertsonian translocations, explaining the multitude of natural Robertsonian populations described in the mouse

    In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis

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    Abstract Background Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo. Results The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery. Conclusions Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.https://deepblue.lib.umich.edu/bitstream/2027.42/146540/1/12951_2018_Article_425.pd

    Characterization of a Clp Protease Gene Regulator and the Reaeration Response in Mycobacterium tuberculosis

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    Mycobacterium tuberculosis (MTB) enters a non-replicating state when exposed to low oxygen tension, a condition the bacillus encounters in granulomas during infection. Determining how mycobacteria enter and maintain this state is a major focus of research. However, from a public health standpoint the importance of latent TB is its ability to reactivate. The mechanism by which mycobacteria return to a replicating state upon re-exposure to favorable conditions is not understood. In this study, we utilized reaeration from a defined hypoxia model to characterize the adaptive response of MTB following a return to favorable growth conditions. Global transcriptional analysis identified the ∼100 gene Reaeration Response, induced relative to both log-phase and hypoxic MTB. This response includes chaperones and proteases, as well as the transcription factor Rv2745c, which we characterize as a Clp protease gene regulator (ClgR) orthologue. During reaeration, genes repressed during hypoxia are also upregulated in a wave of transcription that includes genes crucial to transcription, translation and oxidative phosphorylation and culminates in bacterial replication. In sum, this study defines a new transcriptional response of MTB with potential relevance to disease, and implicates ClgR as a regulator involved in resumption of replication following hypoxia

    FE65 Binds Teashirt, Inhibiting Expression of the Primate-Specific Caspase-4

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    The Alzheimer disease (AD) amyloid protein precursor (APP) can bind the FE65 adaptor protein and this complex can regulate gene expression. We carried out yeast two-hybrid studies with a PTB domain of FE65, focusing on those genes that might be involved in nuclear signaling, and identified and validated Teashirt proteins as FE65 interacting proteins in neurons. Using reporter systems, we observed that FE65 could simultaneously recruit SET, a component of the inhibitor of acetyl transferase, and Teashirt, which in turn recruited histone deacetylases, to produce a powerful gene-silencing complex. We screened stable cell lines with a macroarray focusing on AD-related genes and identified CASP4, encoding caspase-4, as a target of this silencing complex. Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. Expression studies in postmortem samples demonstrated decreasing expression of Teashirt and increasing expression of caspase-4 with progressive cognitive decline. Importantly, there were significant increases in caspase-4 expression associated with even the earliest neuritic plaque changes in AD. We evaluated a case-control cohort and observed evidence for a genetic association between the Teashirt genes TSHZ1 and TSHZ3 and AD, with the TSHZ3 SNP genotype correlating with expression of Teashirt3. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD. Thus the cell biological, gene expression and genetic data support a role for Teashirt/caspase-4 in AD biology. As caspase-4 shows evidence of being a primate-specific gene, current models of AD and other neurodegenerative conditions may be incomplete because of the absence of this gene in the murine genome

    Spatial and Sex-Specific Variation in Growth of Albacore Tuna (Thunnus alalunga) across the South Pacific Ocean

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    Spatial variation in growth is a common feature of demersal fish populations which often exist as discrete adult sub-populations linked by a pelagic larval stage. However, it remains unclear whether variation in growth occurs at similar spatial scales for populations of highly migratory pelagic species, such as tuna. We examined spatial variation in growth of albacore Thunnus alalunga across 90° of longitude in the South Pacific Ocean from the east coast of Australia to the Pitcairn Islands. Using length-at-age data from a validated ageing method we found evidence for significant variation in length-at-age and growth parameters (L∞ and k) between sexes and across longitudes. Growth trajectories were similar between sexes up until four years of age, after which the length-at-age for males was, on average, greater than that for females. Males reached an average maximum size more than 8 cm larger than females. Length-at-age and growth parameters were consistently greater at more easterly longitudes than at westerly longitudes for both females and males. Our results provide strong evidence that finer spatial structure exists within the South Pacific albacore stock and raises the question of whether the scale of their “highly migratory” nature should be re-assessed. Future stock assessment models for South Pacific albacore should consider sex-specific growth curves and spatial variation in growth within the stock

    Effect and cost of an after-school dance programme on the physical activity of 11-12 year old girls: The Bristol Girls Dance Project, a school-based cluster randomised controlled trial

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    © 2015 Jago et al. Background: The aim of this study was to examine the effectiveness and cost of an after-school dance intervention at increasing the physical activity levels of Year 7 girls (age 11-12). Methods: A cluster randomised controlled trial was conducted in 18 secondary schools. Participants were Year 7 girls attending a study school. The Bristol Girls Dance Project (BGDP) intervention consisted of up to forty, 75-minute dance sessions delivered in the period immediately after school by experienced dance instructors over 20-weeks. The pre-specified primary outcome was accelerometer assessed mean minutes of weekday moderate to vigorous physical activity (MVPA) at time 2 (52weeks are T0 baseline assessments). Secondary outcomes included accelerometer assessed mean minutes of weekday MVPA at time 1 (while the intervention was still running) and psychosocial outcomes. Intervention costs were assessed. Results: 571 girls participated. Valid accelerometer data were collected from 549 girls at baseline with 508 girls providing valid accelerometer data at baseline and time 2. There were no differences between the intervention and control group for accelerometer assessed physical activity at either time 1 or time 2. Only one third of the girls in the intervention arm met the pre-set adherence criteria of attending two thirds of the dance sessions that were available to them. Instrumental variable regression analyses using complier average causal effects provided no evidence of a difference between girls who attended the sessions and the control group. The average cost of the intervention was £73 per girl, which was reduced to £63 when dance instructor travel expenses were excluded. Conclusion: This trial showed no evidence that an after-school dance programme can increase the physical activity of Year 7 girls. The trial highlighted the difficulty encountered in maintaining attendance in physical activity programmes delivered in secondary schools. There is a need to find new ways to help adolescent girls to be physically active via identifying ways to support and encourage sustained engagement in physical activity over the life course. Trial registration: ISRCTN5288252

    Palatal development of preterm and low birthweight infants compared to term infants – What do we know? Part 2: The palate of the preterm/low birthweight infant

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    BACKGROUND: Well-designed clinical studies on the palatal development in preterm and low birthweight infants are desirable because the literature is characterized by contradictory results. It could be shown that knowledge about 'normal' palatal development is still weak as well (Part 1). The objective of this review is therefore to contribute a fundamental analysis of methodologies, confounding factors, and outcomes of studies on palatal development in preterm and low birthweight infants. METHODS: An electronic literature search as well as hand searches were performed based on Cochrane search strategies including sources of more than a century in English, German, and French. Original data were recalculated from studies which primarily dealt with both preterm and term infants. The extracted data, especially those from non-English paper sources, were provided unfiltered for comparison. RESULTS: Seventy-eight out of 155 included articles were analyzed for palatal morphology of preterm infants. Intubation, feeding tubes, feeding mode, tube characteristics, restriction of oral functions, kind of diet, cranial form and birthweight were seen as causes contributing to altered palatal morphology. Changes associated with intubation concern length, depth, width, asymmetry, crossbite, and contour of the palate. The phenomenon 'grooving' has also been described as a complication associated with oral intubation. However, this phenomenon suffers from lack of a clear-cut definition. Head flattening, pressure from the oral tube, pathologic or impaired tongue function, and broadening of the alveolar ridges adjacent to the tube have been raised as causes of 'grooving'. Metrically, the palates of intubated preterm infants remain narrower, which has been examined up to the age of the late mixed dentition. CONCLUSION: There is no evidence that would justify the exclusion of any of the raised causes contributing to palatal alteration. Thus, early orthodontic and logopedic control of formerly orally intubated preterm infants is recommended, as opposed to non-intubated infants. From the orthodontic point of view, nasal intubation should be favored. The role that palatal protection plates and pressure-dispersing pads for the head have in palatal development remains unclear
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