BackgroundRegulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45–1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction. To understand how SR45 is involved in the regulation of reproductive processes, we studied mRNA from the wild-type and sr45–1 inflorescences using RNA-seq, and identified SR45-bound RNAs by immunoprecipitation.ResultsUsing a variety of bioinformatics tools, we identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45-dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs (SARs). There is little overlap between SDR genes and SAS genes, and neither set of genes is enriched for flower or seed development. However, transcripts from reproductive process genes are significantly overrepresented in SARs. In exploring the fate of SARs, we found that a total of 81 SARs are subject to alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD) targets. Motifs related to GGNGG are enriched both in SARs and near different types of SAS events, suggesting that SR45 recognizes this motif directly. Genes involved in plant defense are significantly over-represented among genes whose expression is suppressed by SR45, and sr45–1 plants do indeed show enhanced immunity.ConclusionWe find that SR45 is a suppressor of innate immunity. We find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45 and in sequences near SR45- dependent alternative splicing events in inflorescence tissue. We find that the alternative splicing events regulated by SR45 are enriched for this motif whether the effect of SR45 is activation or repression of the particular event. Thus, our data suggests that SR45 acts to control splice site choice in a way that defies simple categorization as an activator or repressor of splicing.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4183-7) contains supplementary material, which is available to authorized users.
The publication of the AAN Practice Parameter was associated with improvement in the standard of care. Most cases in the database come from specialized ALS centers, and further information on the community care of ALS patients is needed.
Objectives: Assessing the effects of diabetes mellitus (DM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-dependent diabetes mellitus (IDDM) on revision TKA (rTKA) has become increasingly imperative due to the increased rates of revisions associated with DM. This study sought to identify complications in rTKA that were independently associated with NIDDM/IDDM compared to nondiabetic (Non-DM) patients and whether IDDM was associated with specific postoperative complications compared to NIDDM. Methods and materials: 16,428 rTKA patients were identified from the ACS-NSQIP database from 2005 to 2016 and stratified into three separate cohorts. 12,922 (78.66%) were Non-DM, 2335 (14.21%) had NIDDM, and 1171 (7.13%) had IDDM. Univariate analyses were utilized to assess for differences in demographics, preoperative comorbidities, and postoperative complication rates. Multivariate logistic regression analyses were then employed to control for significant differences in patients characteristics to assess NIDDM and IDDM as independent risk factors for complications in comparison to Non-DM. IDDM was further analyzed as a risk factor in comparison to NIDDM for the purpose of elucidating the impact of insulin dependence on risk for postoperative complications. Results: NIDDM was an independent risk factor for deep incisional surgical site infections (Odds Ratio (OR): 2.477) and urinary tract infections (UTI) (OR 1.862) (p < 0.05). Compared to NIDDM, IDDM was independently associated with greater risk for pneumonia (OR 2.603), septic shock (OR 6.597), blood transfusions (OR 1.326), and an extended length of stay (OR: 1.331) (p < 0.05). IDDM additionally increased the risk for acute renal failure (OR 3.269) and cardiac arrest (OR 3.268) (p < 0.05) when compared to Non-DM. DM patients overall had increased rates of worse outcomes and infectious complications. Conclusion: Although differences between diabetes and non-diabetes rTKA patients were seen, differences in complication rates between diabetes patients further divided based on insulin dependence status were also noted. Future work examining whether targeting perioperative glucose levels <200 mg/ dL in DM rTKA patients decreases infectious complications is warranted. Future work analyzing the role of tranexamic acid administration and 24-h postoperative antibiotics in rTKA IDDM patients may be warranted given the elevated risk of pneumonia, septic shock, and blood transfusions.
Emphysematous osteomyelitis (EO) is a rare infection associated with intraosseous gas. EO is an often fatal disease with an estimated 34% mortality. We present a case of a 63-year-old man with sternoclavicular EO with pleural involvement and significant subcutaneous emphysema diagnosed by CT. Extension of intraosseous gas into the pleural cavity is an extremely interesting presentation that has not been previously reported. The patient underwent a multidisciplinary treatment approach with surgical debridement and an extended antibiotic course. Intraoperative cultures of the pectoralis muscle and bone biopsy grew pan-sensitive Escherichia coli. Prompt recognition and treatment are paramount to avoid a potentially fatal outcome. A review of the literature of the previous 46 cases of EO is presented for associated risk factors, the role of surgical management and antibiotic therapy.
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