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Dorsal root ganglia (DRG) at all levels of the spinal cord are a prominent target of Friedreich ataxia (FA). The lesions include hypoplasia of neurons, proliferation of satellite cells, infiltration by IBA- 1-reactive monocytes, and formation of residual nodules. Paucity and smallness of DRG neurons account for the lack of large myelinated axons in dorsal roots and sensory peripheral nerves. The lack of myelin in dorsal roots can be attributed to low levels of neuregulin 1 type III (NRG1[III]). Lysates of 13 DRG of genetically confirmed FA patients were analyzed by antibody microarray with 878 different validated antibodies that target structural and signaling proteins, and by Western blots. KIT and mTOR, two proteins involved in cellular proliferation, were significantly upregulated in the DRG of FA. KIT is a transmembrane receptor that dimerizes when it binds two molecules of stem cell factor (SCF) in its extracellular domain and becomes activated as protein tyrosine kinase. Immunohistochemistry with anti-KIT generated reaction product in satellite cells of normal DRG and prominent labeling of these cells in FA that co-localized with SCF on double- label immunofluorescence; SCF was present in S100-positive satellite cells rather than monocytes. Immunohistochemical reaction product of mTOR and other mTOR complex proteins, such as hamartin (TSC1), tuberin (TSC2), raptor (mTOR complex 1) and rictor (mTOR complex 2) was also present in satellite cells of normal DRG and DRG of FA. Antibodies to two downstream proteins that are considered to be indicators of mTOR activity, P70 S6K and 4E-binding protein 1, revealed no reaction product in DRG of FA. TSC1, TSC2, and mTOR are best known from their roles in tuberous sclerosis, but expression of these proteins, and KIT, in DRG may contribute to signaling cascades underlying the proliferation of satellite cells in FA.
This presentation will enable the learner to:
1. Discuss cellular proliferation in the pathogenesis of the DRG lesion in Friedreich ataxia
CONFLICT OF INTEREST
AHK is a consultant to PTC Therapeutics of South Plainfield, NJ USA. SP and CS are majority owners of Kinexus.
Potential secondary influences on titanium distribution should be evaluated when using ash beds as volcanic source indicators and for correlation purposes. In this study, well-correlated altered ash beds in Permian–Triassic boundary (PTB) successions of various facies in South China were investigated to better understand their use in source discrimination and stratigraphic correlation. The ash beds deposited in lacustrine and paludal facies contain significantly more Ti relative to deposits in marine facies. Neoformed anatase grains nanometres to micrometres in size are associated closely with clay minerals, whereas detrital anatase was observed in the remnants of altered ash beds of terrestrial facies. Extraction of the clay fraction of altered ash beds may exclude significantly detrital accessory minerals such as anatase and rutile added during sediment reworking, and the concentrations of immobile elements in the clay fraction may therefore be used to interpret more effectively their source igneous rocks.
Precise instrumental calibration is of crucial importance to 21-cm cosmology experiments. The Murchison Widefield Array’s (MWA) Phase II compact configuration offers us opportunities for both redundant calibration and sky-based calibration algorithms; using the two in tandem is a potential approach to mitigate calibration errors caused by inaccurate sky models. The MWA Epoch of Reionization (EoR) experiment targets three patches of the sky (dubbed EoR0, EoR1, and EoR2) with deep observations. Previous work in Li et al. (2018) and (2019) studied the effect of tandem calibration on the EoR0 field and found that it yielded no significant improvement in the power spectrum (PS) over sky-based calibration alone. In this work, we apply similar techniques to the EoR1 field and find a distinct result: the improvements in the PS from tandem calibration are significant. To understand this result, we analyse both the calibration solutions themselves and the effects on the PS over three nights of EoR1 observations. We conclude that the presence of the bright radio galaxy Fornax A in EoR1 degrades the performance of sky-based calibration, which in turn enables redundant calibration to have a larger impact. These results suggest that redundant calibration can indeed mitigate some level of model incompleteness error.
We present the elements required to construct two devices used in an undergraduate plasma physics laboratory. The materials and construction costs of the sources, the vacuum systems and probe drives and electrical circuits are presented in detail in the text and the first appendix. We also provide the software for probe motion and data acquisition as well as the electrical schematics for key components. Experiments which have been performed are listed and two (resonance cones and whistler waves) are described in greater detail. The machines are flexible and original research is possible.
Increasing evidence supports that 5HTTLPR polymorphism of the serotonin transporter gene(5HTTLPR) might associate to bipolar disorder and affective temperaments as measured by TEMPS-A. But the results are discrepant, furthermore, there are no data from Chinese population.
The present study was designed to investigate association between 5HTTLPR and bipolar disorder and affective temperaments of patients with bipolar disorder in the specific Chinese population and add new evidence to the field.
There hundred and five patients with bipolar disorder and 272 normal controls were included in the present case-control study⌧Temperament Evaluation of Memphis, Pisa, Paris and San Diego -autoquestionnaire version (TEMPS-A) in Chinese was used to assess affective temperament. Chi-square test, T test, Nonparametric test and ANOVA were employed to explore association between 5HTTLPR polymorphism and bipolar disorder and affective temperament of patients with bipolar disorder.
5-HTTLPR L/S polymorphism was associated with bipolar disorder in female (genotype χ2 = 6.769⌧P = 0.034⌧allele χ2 = 6.028⌧P = 0.014) and the S allele was associated with anxious temperament (t = 8.248⌧P = 0.005) in patients with bipolar disorder. the LA allele of 5-HTTLPR rs25531 A/G polymorphism was associated with hyperthymic temperament in patients with bipolar disorder (Z = −2.205⌧P = 0.027).
5-HTTLPR might have an effect on the prevalence of bipolar disorder in female and regulate affective temperaments of patients with bipolar disorder in some degree in Chinese population.
To explore the relationship between resilience and social support, coping style of children in two middle schools for providing an evidence for improving childrens’resilience.
Six hundred childrens were surveyed with the Connor-Davidson resilience questionnaire(CD-RISC), perceived social support scale(PSSS)and coping style questionnaire (CSQ).
Resilience had significant difference between male and female children.
The resilience was positively correlated with social support and two factors of coping style: seeking help and solving problem, but negatively correlated with the other factors in coping style questionnaire.
Children with high score in Connor-Davidson resilience questionnaire are more tend to the positive coping style.
Social support is an important factor of resilience in children.
White-light continuum can be induced by the interaction of intense femtosecond laser pulses with condensed materials. By using two orthogonal polarizers, a self-induced birefringence of continuum is observed when focusing femtosecond laser pulses into bulk fused silica. That is, the generated white-light continuum is synchronously modulated anisotropically while propagating in fused silica. Time-resolved detection confirms that self-induced birefringence of continuum shows a growth and saturation feature with time evolution. By adjusting laser energy, the transmitted intensity of continuum modulated by self-induced birefringence also varies correspondingly. Morphology analysis with time evolution indicates that it is the focused femtosecond laser pulses that induce anisotropic microstructures in bulk fused silica, and the anisotropic structures at the same time modulate the generated continuum.
Nikolaus Friedreich (1877) was aware of heart disease in his patients but thought it was unrelated to the neurological disorder. In 1946, Dorothy Russell considered cardiomyopathy an integral part of Friedreich ataxia (FA). In addition to sparse inflammatory infiltration, sections show fibrosis and capillary hyperplasia. We examined the left ventricular walls of 41 homozygous FA patients aged 10–87 and 21 controls aged 2–69. An antibody to CD34 enabled quantitative capillary profile counts for a comparison with cardiomyocyte counts in the same field. Mean capillary counts in normals were 1926±341/mm2, and the median ratio of capillaries to cardiomyocytes was 1.0 (interquartile range [IQR]: 0.9-1.2). In FA, however, the number of cardiomyocytes/mm2 was less, and the median ratio of capillaries to heart fibers was 2.0 (IQR 1.4-2.4). There was a significant correlation of the higher guanine-adenine-adenine trinucleotide length (shorter allele, GAA1) with the younger age of onset, shorter disease duration, and lower cardiomyocyte counts. The ratio of capillaries to heart fibers was higher in patients with long GAA1 repeat expansions (e.g., 3.31 in GAA1 of 1200). Double-label immunofluorescence for CD34 and S100A4 revealed co-expression in endothelial cells, supporting endothelial-to-mesenchymal transition in the pathogenesis of cardiac fibrosis (supported by Friedreich’s Ataxia Research Alliance).
The presentation will enable the learner to:
1. Describe endothelial-to-mesenchymal transition in the pathogenesis of cardiac fibrosis in Friedreich cardiomyopathy
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of
was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
TiO2 nanomaterials with platelet or nanosheet morphologies can offer improved properties for photocatalytic applications, but established methods to produce them typically require structure-directing agents since anatase-phase TiO2 does not have a layered structure. In the present work, the preparation of TiO2 nanosheets by the chemical oxidation of TiS2 nanosheets is demonstrated. Electrochemical exfoliation of bulk TiS2 into TiS2 nanosheets, followed by the hydrothermal treatment at 180 °C for 14 h is performed. The results show that polycrystalline TiO2 nanosheets with the anatase structure are formed, and that the nanosheet morphology can still be maintained after the hydrothermal treatment. The TiO2 nanosheets show good photocatalytic activity for the degradation of methylene blue, but the performance is negatively affected by the residual carbon black that was needed in the TiS2 electrode to enable electrochemical exfoliation. These results show that conversion of TiS2 nanosheets to TiO2 nanosheets is a promising synthetic strategy but highlights how the interfacial properties of the obtained materials could be affected by ancillary components in the preparation method.
We re-analyzed OJ287 in 120 Very Long Baseline Array (VLBA, MOJAVE) observations (at 15 GHz) covering the time span between Apr. 1995 and Apr. 2017. We find that the radio jet motion over the sky is consistent with a precessing and nutating jet source. The variability of the radio flux-density can be explained by Doppler beaming due to a change in the viewing angle. We suggest that part of the optical emission is due to synchrotron emission related to the jet radiation. We find a strikingly similar scaling for the timescales for precession and nutation as indicated for SS433 with a factor of roughly 50 times longer in OJ287.
Spatiotemporal analysis is an important tool to monitor changes of tuberculosis (TB) epidemiology, identify high-risk regions and guide resource allocation. However, there are limited data on the contributing factors of TB incidence. This study aimed to investigate the spatiotemporal pattern of TB incidence and its associated factors in mainland China during 2005–2013. Global Moran's I test, Getis-Ord Gi index and heat maps were used to examine the spatial clustering and seasonal patterns. Generalized Linear Mixed Model was applied to identify factors associated with TB incidence. TB incidence presented high geographical variations with two main hot spots, while a generally consistent seasonal pattern was observed with a peak in late winter. Furthermore, we found province-level TB incidence increased with the proportion of the elderly but decreased with Gross Demographic Product per capita and the male:female ratio. Meteorological factors also influenced TB incidence. TB showed obvious spatial clustering in mainland China and both the demographic and socio-economic factors and meteorological measures were associated with TB incidence. These results provide the related information to identify the high-risk districts and the evidence for the government to develop corresponding control measures.
We investigated the first presence of qnrA among Shigella sonnei clinical isolates in Jiangsu Province, China. The qnrA-positive isolates coexisted with the mutation in gyrA at codon 83, these isolates were resistant to nalidixic acid and 22·2% (2 of 9) of them were resistant to norfloxacin.
The E2F transcription factor family is distributed widely in eukaryotes and has been well studied among mammals. In the present study, the E2F transcription factor 4 (E2F4) gene was isolated from fat bodies of Antheraea pernyi and sequenced. E2F4 comprised a 795 bp open reading frame encoding a deduced amino acid sequence of 264 amino acid residues. The recombinant protein was expressed in Escherichia coli (Transetta DE3), and anti-E2F4 antibodies were prepared. The deduced amino acid sequence displayed significant homology to an E2F4-like protein from Bombyx mori L. Quantitative real-time polymerase chain reaction analysis revealed that E2F4 expression was highest in the integument, followed by the fat body, silk glands, and haemocytes. The expression of E2F4 was upregulated in larvae challenged by bacterial (Escherichia coli, Micrococcus luteus), viral (nuclear polyhedrosis virus), and fungal (Beauveria bassiana) pathogens. These observations indicated that E2F4 is an inducible protein in the immune response of A. pernyi and probably in other insects.
A series of catalytic reactions has been performed in our laboratory using olivine-type silicates (OTS) and SiC as catalysts for the conversion of carbon-containing molecules (such as acetylene, CO and methanol) to small organic molecules (C2H4, C3H3, CH3O) and also polycyclic aromatic hydrocarbons (PAHs). Experimentally, small-to-medium-sized gas-phase compounds such as PAHs, reaction intermediates and hydrocarbon compounds were detected in situ using the time-of-light mass-spectrometry technique. Solid deposition on the catalyst surface was examined by high-resolution transmission electron microscopy and thermo-gravimetric analysis techniques. Our laboratory results show that the conversion of acetylene to PAHs, the CO disproportionation reaction for producing CO2 and carbon deposition (graphitic and carbon nanostructures), and also the transformation of methanol to hydrocarbon compounds can easily be achieved with OTS as a catalyst. Furthermore, the conversion of acetylene to PAHs could also be achieved by SiC as the catalyst. It is proposed that these catalytic reactions mimic similar chemical processes in circumstellar envelopes (CSEs).
For this study, threonine (Thr) deficiency was hypothesised to exacerbate the intestinal damage induced by feed withdrawal with coccidial infection because of its high obligatory requirement by the gut; two dietary Thr treatments (0·49 and 0·90 %) were applied to chicks from 0 to 21 d of age. At 13 d of age, feed was withdrawn for 24 h from one-half of birds of each dietary treatment with subsequent gavage of a 25× dose of coccidial vaccine. Overall, there were four treatments with eight replicate cages per treatment. Under combined challenge, birds fed the Thr-deficient diet had 38 % lower 13–21-d body weight gain (P≤0·05) compared with birds fed the Thr-control diet. At 21 d, the challenged group fed low Thr had higher number of oocysts (+40 %, P=0·03) and lower crypt depth (−31 %, P<0·01). In addition, birds fed the low-Thr diet had higher gut permeability as measured after 2 h of administration of fluorescein isothiocyanate-dextran (3–5 kDa, P<0·01), which may be attributed to decreased IgA production (P=0·03) in the ileum. In caecal tonsils, the challenged group fed low Thr had lower CD3:Bu-1 ratio (P≤0·05), along with a tendency for lower CCR9 mRNA expression in birds fed the low-Thr diet (P=0·10). In addition, Thr deficiency tended to increase IL-10 mRNA expression regardless of infection (P=0·06), but did not change interferon-γ mRNA expression upon coccidial infection (P>0·05). Overall, Thr deficiency worsened the detrimental effects of combined feed withdrawal and coccidial infection on growth performance and oocyst shedding by impairing intestinal morphology, barrier function, lymphocyte profiles and their cytokine expressions.