197 research outputs found
Tibial torus and toddler's fractures misdiagnosed as transient synovitis: a case series
<p>Abstract</p> <p>Introduction</p> <p>The high incidence of transient synovitis in early childhood makes it the first suspected pathology in a limping child. Trauma, which has long been regarded as a causative factor for transient synovitis, may be underestimated in a non-cooperative toddler.</p> <p>After excluding most serious conditions, such as septic arthritis, a speculative diagnosis of transient synovitis can be made, and this can easily mask a subtle musculoskeletal injury.</p> <p>Case presentations</p> <p>We report the cases of three Caucasian patients (two boys, aged 20-months- and three-years-old, and one girl, aged two-years-old), with tibial torus and toddler's fractures which were late-diagnosed due to an initial misdiagnosis of transient synovitis of the hip.</p> <p>Conclusion</p> <p>In a non-cooperative child musculoskeletal trauma can be mistaken as a simple causative factor for transient synovitis of the hip and this can easily prevent further investigation for a possible subtle musculoskeletal injury of the lower extremities.</p> <p>Our experience with the presented cases suggests the need to be more vigilant in the differential diagnosis of transient synovitis in young children.</p
Secular Evolution and the Growth of Pseudobulges in Disk Galaxies
Galaxy evolution is in transition from an early universe dominated by
hierarchical clustering to a future dominated by secular processes. These
result from interactions involving collective phenomena such as bars, oval
disks, spiral structure, and triaxial dark halos. This paper summarizes a
review by Kormendy & Kennicutt (2004) using, in part, illustrations of
different galaxies. In simulations, bars rearrange disk gas into outer rings,
inner rings, and galactic centers, where high gas densities feed starbursts.
Consistent with this picture, many barred and oval galaxies have dense central
concentrations of gas and star formation rates that can build bulge-like
stellar densities on timescales of a few billion years. We conclude that
secular evolution builds dense central components in disk galaxies that look
like classical, merger-built bulges but that were made slowly out of disk gas.
We call these pseudobulges. Many pseudobulges can be recognized because they
have characteristics of disks: (1) flatter shapes than those of classical
bulges, (2) correspondingly large ratios of ordered to random velocities, (3)
small velocity dispersions, (4) spiral structure or nuclear bars, (5) nearly
exponential brightness profiles, and (6) starbursts. These structures occur
preferentially in barred and oval galaxies in which secular evolution should be
most rapid. Thus a variety of observational and theoretical results contribute
to a new paradigm of secular evolution that complements hierarchical
clustering.Comment: 19 pages, 9 Postscript figures; requires kapproc.cls and procps.sty;
to appear in "Penetrating Bars Through Masks of Cosmic Dust: The Hubble
Tuning Fork Strikes a New Note", ed. Block, Freeman, Puerari, Groess, and
Block, Dordrecht: Kluwer, in press; for a version with full resolution
figures, see http://chandra.as.utexas.edu/~kormendy/ar3ss.htm
The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain
CFP1 is a CXXC domain-containing protein and an essential component of the SETD1 histone H3K4 methyltransferase complex. CXXC domain proteins direct different chromatin-modifying activities to various chromatin regions. Here, we report crystal structures of the CFP1 CXXC domain in complex with six different CpG DNA sequences. The crescent-shaped CFP1 CXXC domain is wedged into the major groove of the CpG DNA, distorting the B-form DNA, and interacts extensively with the major groove of the DNA. The structures elucidate the molecular mechanism of the non-methylated CpG-binding specificity of the CFP1 CXXC domain. The CpG motif is confined by a tripeptide located in a rigid loop, which only allows the accommodation of the non-methylated CpG dinucleotide. Furthermore, we demonstrate that CFP1 has a preference for a guanosine nucleotide following the CpG motif
Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline
The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline
A Downstream CpG Island Controls Transcript Initiation and Elongation and the Methylation State of the Imprinted Airn Macro ncRNA Promoter
A CpG island (CGI) lies at the 5′ end of the Airn macro non-protein-coding (nc) RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs) occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start
Clustering of Codons with Rare Cognate tRNAs in Human Genes Suggests an Extra Level of Expression Regulation
In species with large effective population sizes, highly expressed genes tend to be encoded by codons with highly abundant cognate tRNAs to maximize translation rate. However, there has been little evidence for a similar bias of synonymous codons in highly expressed human genes. Here, we ask instead whether there is evidence for the selection for codons associated with low abundance tRNAs. Rather than averaging the codon usage of complete genes, we scan the genes for windows with deviating codon usage. We show that there is a significant over representation of human genes that contain clusters of codons with low abundance cognate tRNAs. We name these regions, which on average have a 50% reduction in the amount of cognate tRNA available compared to the remainder of the gene, RTS (rare tRNA score) clusters. We observed a significant reduction in the substitution rate between the human RTS clusters and their orthologous chimp sequence, when compared to non–RTS cluster sequences. Overall, the genes with an RTS cluster have higher tissue specificity than the non–RTS cluster genes. Furthermore, these genes are functionally enriched for transcription regulation. As genes that regulate transcription in lower eukaryotes are known to be involved in translation on demand, this suggests that the mechanism of translation level expression regulation also exists within the human genome
Human Placental-Specific Epipolymorphism and its Association with Adverse Pregnancy Outcomes
Interindividual variation in DNA-methylation level is widespread in the human genome, despite its critical role in regulating gene expression. The nature of this variation, including its tissue-specific nature, and the role it may play in human phenotypic variation and disease is still poorly characterized. The placenta plays a critical role in regulating fetal growth and development in ways that have lifelong effects on health. To identify genes with a high degree of interindividual DNA methylation variation in the human placenta, we surveyed the human genome using the Illumina GoldenGate Methylation Cancer panel targeting 1505 CpG sites of 807 genes. While many sites show a continuous pattern of methylation levels, WNT2, TUSC3 and EPHB4 were identified to have a polymorphic “on-or-off” pattern of DNA methylation variation at their promoter region which was confirmed by pyrosequencing. Methylation of these genes can be found in 7%–25% of over 100 placentas tested. The methylation state at the promoter of these genes is concordant with mRNA allelic expression. In three informative cases TUSC3 was observed to be methylated on the maternal allele, and it is thus possible this represents a polymorphically imprinted gene. Furthermore, TUSC3 promoter methylation showed evidence for association with preeclampsia. A biological significance of these methylation allelic polymorphisms (MAPs) to human placental diversity is further implied by their placental specificity and absence in mouse. An extended study of blood suggests that MAPs may also be found in other tissues, implicating their utility for tissue-specific association with complex disorders. The identification of such “epipolymorphism” in other tissues and their use in association studies, should improve our understanding of interindividual phenotypic variability and complex disease susceptibility
Ontogeny of CpG island methylation and specificity of DNMT3 methyltransferases during embryonic development in the mouse
Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production
BACKGROUND: As critical mediators of local and systemic inflammatory responses, cytokines are produced in the brain following ischaemic stroke. Some have been detected in the circulation of stroke patients, but their role and source is unclear. Focusing primarily on interleukin(IL)-1-related mechanisms, we serially measured plasma inflammatory markers, and the production of cytokines by whole blood, from 36 patients recruited within 12 h and followed up to 1 year after acute ischaemic stroke (AIS). RESULTS: Admission plasma IL-1 receptor antagonist (IL-1ra) concentration was elevated, relative to age-, sex-, and atherosclerosis-matched controls. IL-1β, soluble IL-1 receptor type II, tumour necrosis factor (TNF)-α, TNF-RII, IL-10 and leptin concentrations did not significantly differ from controls, but peak soluble TNF receptor type I (sTNF-RI) in the first week correlated strongly with computed tomography infarct volume at 5–7 days, mRS and BI at 3 and 12 months. Neopterin was raised in patients at 5–7 d, relative to controls, and in subjects with significant atherosclerosis. Spontaneous IL-1β, TNF-α and IL-6 gene and protein expression by blood cells was minimal, and induction of these cytokines by lipopolysaccharide (LPS) was significantly lower in patients than in controls during the first week. Minimum LPS-induced cytokine production correlated strongly with mRS and BI, and also with plasma cortisol. CONCLUSION: Absence of spontaneous whole blood gene activation or cytokine production suggests that peripheral blood cells are not the source of cytokines measured in plasma after AIS. Increased plasma IL-1ra within 12 h of AIS onset, the relationship between sTNF-RI and stroke severity, and suppressed cytokine induction suggests early activation of endogenous immunosuppressive mechanisms after AIS
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