Abstract Spinal cord injury (SCI) leads to formation of a fibrotic scar that is inhibitory to axon regeneration. Recent evidence indicates that the fibrotic scar is formed by perivascular ...fibroblasts, but the mechanism by which they are recruited to the injury site is unknown. Using bone marrow transplantation in mouse model of spinal cord injury, we show that fibroblasts in the fibrotic scar are associated with hematogenous macrophages rather than microglia, which are limited to the surrounding astroglial scar. Depletion of hematogenous macrophages results in reduced fibroblast density and basal lamina formation that is associated with increased axonal growth in the fibrotic scar. Cytokine gene expression analysis after macrophage depletion indicates that decreased Tnfsf8, Tnfsf13 (tumor necrosis factor superfamily members) and increased BMP1-7 (bone morphogenetic proteins) expression may serve as anti-fibrotic mechanisms. Our study demonstrates that hematogenous macrophages are necessary for fibrotic scar formation and macrophage depletion results in changes in multiple cytokines that make the injury site less fibrotic and more conducive to axonal growth.
We determine the local metallicity of the ionized gas for more than 9.2 × 105 star-forming regions (spaxels) located in 1023 nearby galaxies included in the Sloan Digital Sky Survey-IV MaNGA integral ...field spectroscopy unit survey. We use the dust extinction derived from the Balmer decrement and the stellar template fitting in each spaxel to estimate the local gas and stellar mass densities, respectively. We also use the measured rotation curves to determine the local escape velocity (Vesc). We then analyze the relationships between the local metallicity and both the local gas fraction ( ) and Vesc. We find that metallicity decreases with both increasing and decreasing Vesc. By examining the residuals in these relations we show that the gas fraction plays a more primary role in the local chemical enrichment than does Vesc. We show that the gas-regulator model of chemical evolution provides a reasonable explanation of the metallicity on local scales. The best-fit parameters for this model are consistent with the metal loss caused by momentum-driven galactic outflows. We also argue that both the gas fraction and the local escape velocity are connected to the local stellar surface density, which in turn is a tracer of the epoch at which the dominant local stellar population formed.
Summary
Background
Genome‐wide association studies in white and Chinese Han populations have found that the single‐nucleotide polymorphism (SNP) rs610604, at the tumour necrosis factor ...(TNF)‐α‐induced protein 3 (TNFAIP3) locus, is associated with psoriasis, and is also associated with response to TNF blockade in psoriasis.
Aim
To examine whether this SNP is also associated with the clinical traits of psoriasis vulgaris (PV).
Methods
A hospital‐based case–control study was performed, which involved 647 subjects 351 patients with PV and 296 healthy controls (HC). The rs610604 variants were typed using a SNaPshot assay.
Results
Both the G allele and the dominant model genotype (GG + GT) of rs610604 were associated with risk of PV (OR = 1.53; P = 0.01 and OR = 1.68, P < 0.01, respectively). In genotype–phenotype analysis, both the G allele and the GG + GT genotype were also associated with the clinical severity of PV. Severe cases Psoriasis Area and Severity Index (PASI) > 6 had a higher frequency of the G allele and the GG + GT genotype compared with mild cases (PASI ≤ 6) (OR = 2.03, P = 0.001 and OR = 2.46, P < 0.001, respectively). In addition, rs610604 was significantly associated with almost all of the phenotypes in subphenotype–control analyses.
Conclusions
SNP rs610604 in the TNFAIP3 locus is associated with the clinical severity of PV in a Chinese Han population.
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and young adults. Several recent studies have shed new light on the alterations in signalling pathways and the downstream ...effects of these pathway alterations in RMS. Many of these effects converge on the fibroblast growth factor and insulin-like growth-factor pathways. These new findings improve the current understanding of RMS, thus offering novel potential therapeutic targets and strategies that may improve the outcome for patients with RMS.
Summary
By integrating the multilevel biological evidence and bioinformatics analyses, the present study represents a systemic endeavor to identify BMD-associated genes and their roles in skeletal ...metabolism.
Introduction
Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes.
Methods
BMD-associated genes were identified by combining the summary statistic
P
values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential bone mineral density (BMD)-associated variants were evaluated by estimating the correlation of the
P
values of the same single-nucleotide polymorphisms (SNPs)/genes between the two consecutive Genetic Factors for Osteoporosis Studies (GEFOS) with largely overlapping samples.
Results
Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, three novel genes (
UBTF
,
AAAS
, and
C11orf58
) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants.
Conclusions
Gene-based analysis as a supplementary strategy to SNP-based genome-wide association studies, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes.
Recent work has exploited pulsar survey data to identify temporally isolated, millisecond-duration radio bursts with large dispersion measures (DMs). These bursts have been interpreted as arising ...from a population of extragalactic sources, in which case they would provide unprecedented opportunities for probing the intergalactic medium; they may also be linked to new source classes. Until now, however, all so-called fast radio bursts (FRBs) have been detected with the Parkes radio telescope and its 13-beam receiver, casting some concern about the astrophysical nature of these signals. Here we present FRB 121102, the first FRB discovery from a geographic location other than Parkes. FRB 121102 was found in the Galactic anti-center region in the 1.4 GHz Pulsar Arecibo L-band Feed Array (ALFA) survey with the Arecibo Observatory with a DM = 557.4 + or - 2.0 pc cm super(-3), pulse width of 3.0 + or - 0.5 ms, and no evidence of interstellar scattering. The observed delay of the signal arrival time with frequency agrees precisely with the expectation of dispersion through an ionized medium. Despite its low Galactic latitude (b = 0degrees.2), the burst has three times the maximum Galactic DM expected along this particular line of sight, suggesting an extragalactic origin. A peculiar aspect of the signal is an inverted spectrum; we interpret this as a consequence of being detected in a sidelobe of the ALFA receiver. FRB 121102's brightness, duration, and the inferred event rate are all consistent with the properties of the previously detected Parkes bursts.
ABSTRACT
In this work, we study variations in the parabolic scintillation arcs of the binary millisecond pulsar PSR J1643−1224 over five years using the Large European Array for Pulsars (LEAP). The ...two-dimensional (2D) power spectrum of scintillation, called the secondary spectrum, often shows a parabolic distribution of power, where the arc curvature encodes the relative velocities and distances of the pulsar, ionized interstellar medium, and Earth. We observe a clear parabolic scintillation arc, which varies in curvature throughout the year. The distribution of power in the secondary spectra is inconsistent with a single scattering screen, which is fully 1D or entirely isotropic. We fit the observed arc curvature variations with two models: an isotropic scattering screen and a model with two independent 1D screens. We measure the distance to the scattering screen to be in the range 114–223 pc, depending on the model, consistent with the known distance of the foreground large-diameter H ii region Sh 2-27 (112 ± 17 pc), suggesting that it is the dominant source of scattering. We obtain only weak constraints on the pulsar’s orbital inclination and longitude of ascending node, since the scintillation pattern is not very sensitive to the pulsar’s motion and the screen is much closer to the Earth than the pulsar. More measurements of this kind – where scattering screens can be associated with foreground objects – will help to inform the origins and distribution of scattering screens within our galaxy.
ABSTRACT
Using data from the Large European Array for Pulsars, and the Effelsberg telescope, we study the scintillation parameters of the millisecond pulsar PSR J0613−0200 over a 7 yr timespan. The ...‘secondary spectrum’ – the 2D power spectrum of scintillation – presents the scattered power as a function of time delay, and contains the relative velocities of the pulsar, observer, and scattering material. We detect a persistent parabolic scintillation arc, suggesting scattering is dominated by a thin, anisotropic region. The scattering is poorly described by a simple exponential tail, with excess power at high delays; we measure significant, detectable scattered power at times out to ${\sim}5 \, \mu {\rm s}$, and measure the bulk scattering delay to be between 50 to 200 ns with particularly strong scattering throughout 2013. These delays are too small to detect a change of the pulse profile shape, yet they would change the times of arrival as measured through pulsar timing. The arc curvature varies annually, and is well fitted by a one-dimensional scattering screen ${\sim}40{{\ \rm per\ cent}}$ of the way towards the pulsar, with a changing orientation during the increased scattering in 2013. Effects of uncorrected scattering will introduce time delays correlated over time in individual pulsars, and may need to be considered in gravitational wave analyses. Pulsar timing programmes would benefit from simultaneously recording in a way that scintillation can be resolved, in order to monitor the variable time delays caused by multipath propagation.
Cold stress adversely affects plant growth and development. Most temperate plants acquire freezing tolerance by a process called cold acclimation. Here, we focus on recent progress in ...transcriptional, post-transcriptional and post-translational regulation of gene expression that is critical for cold acclimation. Transcriptional regulation is mediated by the inducer of C-repeat binding factor (CBF) expression 1 (ICE1), the CBF transcriptional cascade and CBF-independent regulons during cold acclimation. ICE1 is negatively regulated by ubiquitination-mediated proteolysis and positively regulated by SUMO (small ubiquitin-related modifier) E3 ligase-catalyzed sumoylation. Post-transcriptional regulatory mechanisms, such as pre-mRNA splicing, mRNA export and small RNA-directed mRNA degradation, also play important roles in cold stress responses.
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