Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis

The aim of the is study is to examine the role of serum substance P (SP) levels as a simple biomarker for rheumatoid arthritis (RA) disease activity, its correlation with other markers of disease activity, and with selected clinical parameters. The study comprised 90 RA patients and 24 healthy controls. RA activity was assessed by means of the disease activity 28-C-reactive protein (DAS28-CRP) index and ultrasound power Doppler (USPD) by the German ultrasound score based on seven joints. SP serum values were obtained by means of an ELISA commercial kit. Statistics were achieved by the Student’s t test and Spearman correlation analysis with Bonferroni correction. As a group, RA patients had significantly increased levels of SP compared with healthy controls (p?<?0.0001). SP levels correlated with DAS28-CRP (r =?0.5050, p?<?0.0001), number of tender joints (NTJ, r =?0.4668, p?<?0.0001), number of swollen joints (NSJ, r?=?0.4439, p?<?0.0001), visual analogue scale (VAS, r?=?0.5131, p?<?0.0001). However, SP did not correlate with CRP levels (r?=?0.0468, p?=?0.6613), nor with the USPD (r?=?0.1740, p?=?0.1009). Elevated serum SP is a common feature of RA patients, which also appears to correlate with clinical measurements of disease activity and with subjective clinical data (NTJ and VAS). Thus, although SP is higher in RA patients with high disease activity, it also detects subtle RA disease activity even in patients in apparent remission, which suggests its usefulness for therapeutic decisions.     

Drug‐Coated Balloons: A Safe and Effective Alternative to Drug‐Eluting Stents in Small Vessel Coronary Artery Disease

Background

Drug‐coated balloons (DCB) have been used to treat de novo small vessel coronary disease (SVD), with promising results and shorter dual antiplatelet therapy (DAPT) duration compared to drug‐eluting stents (DES). We compared safety and effectiveness of the two treatments at 1 year.

Methods

We reviewed 3,613 angioplasty cases retrospectively from 2011 to 2013 and identified 335 patients with SVD treated with device diameter of ≤2.5 mm. DCB‐only angioplasty was performed in 172 patients, whereas 163 patients were treated with second‐generation DES.

Results

DCB patients had smaller reference vessel diameter (2.22 ± 0.30 vs. 2.44 ± 0.19 mm, P < 0.001) and received smaller devices (median diameter 2.25 vs. 2.50 mm, P < 0.001) compared to the DES group. DES‐treated vessels had larger acute lumen gain (1.71 ± 0.48 mm) than DCB (1.00 ± 0.53 mm, P < 0.001). Half the patients had diabetes mellitus. While there were more patients presenting with acute coronary syndrome (ACS) in the DCB group (77.9% vs. 62.2%, P = 0.013), they received shorter DAPT (7.4 ± 4.7 vs. 11.8 ± 1.4 months, P < 0.001) than the DES group. The 1‐year composite major adverse cardiac event rate was 11.6% in the DCB arm and 11.7% in the DES arm (P = 1.000), with target lesion revascularization rate of 5.2% and 3.7%, respectively, (P = 0.601).

Conclusions

In this high‐risk cohort of patients, DCB‐only angioplasty delivered good clinical outcome at 1 year. The results were comparable with DES‐treated patients, but had the added benefit of a shorter DAPT regime.

     

The genome of Aiptasia,a sea anemone model for coral symbiosis

The most diverse marine ecosystems, coral reefs, depend upon a functional symbiosis between a cnidarian animal host (the coral) and intracellular photosynthetic dinoflagellate algae. The molecular and cellular mechanisms underlying this endosymbiosis are not well understood, in part because of the difficulties of experimental work with corals. The small sea anemone Aiptasia provides a tractable laboratory model for investigating these mechanisms. Here we report on the assembly and analysis of the Aiptasia genome, which will provide a foundation for future studies and has revealed several features that may be key to understanding the evolution and function of the endosymbiosis. These features include genomic rearrangements and taxonomically restricted genes that may be functionally related to the symbiosis, aspects of host dependence on alga-derived nutrients, a novel and expanded cnidarian-specific family of putative pattern-recognition receptors that might be involved in the animal–algal interactions, and extensive lineage-specific horizontal gene transfer. Extensive integration of genes of prokaryotic origin, including genes for antimicrobial peptides, presumably reflects an intimate association of the animal–algal pair also with its prokaryotic microbiome.Coral reefs form marine-biodiversity hotspots that are of enormous ecological, economic, and aesthetic importance. Coral growth and reef deposition are based energetically on the endosymbiosis between the cnidarian animal hosts and photosynthetic dinoflagellate algae of the genus Symbiodinium, which live in vesicles within the gastrodermal (gut) cells of the animal and typically supply ≥90% of its total energy, while the host provides the algae with a sheltered environment and the inorganic nutrients needed for photosynthesis and growth (1). This tight metabolic coupling allows the holobiont (i.e., the animal host and its microbial symbionts) to thrive in nutrient-poor waters. Although the ecology of coral reefs has been studied intensively, the molecular and cellular mechanisms underlying the critical endosymbiosis remain poorly understood (2). As coral reefs face an ongoing and increasing threat from anthropogenic environmental change (3), new insights into these mechanisms are of critical importance to understanding the resilience and adaptability of coral reefs and thus to the planning of conservation strategies (4).Aiptasia is a globally distributed sea anemone that harbors endosymbiotic Symbiodinium like its Class Anthozoa relatives the stony corals (Fig. 1 and SI Appendix, Fig. S1A) (4, 5). Aiptasia has a range of polyp sizes convenient for experimentation and is easily grown in laboratory culture, where it reproduces both asexually (so that large clonal populations can be obtained) and sexually (allowing experiments on larvae and potentially genetic studies), and it can be maintained indefinitely in an aposymbiotic (dinoflagellate-free) state and reinfected by a variety of Symbiodinium strains (6, 7). These characteristics make Aiptasia a highly attractive model system for studies of the molecular and cellular basis of the cnidarian–dinoflagellate endosymbiosis (2, 4). To provide a solid platform for research on Aiptasia, we have sequenced and analyzed its genome. The results have already provided important insights into several aspects of the evolution and function of the symbiotic system.Open in a separate windowFig. 1.Phylogenetic position and different symbiotic states of Aiptasia. (A) Partial phylogenetic tree (see SI Appendix, SI Materials and Methods and Fig. S1A for details) shows Aiptasia grouped with other anthozoans among the cnidarians. Numbers on nodes denote bootstrap values. (B–D) An aposymbiotic Aiptasia polyp (B) and symbiotic polyps viewed under white light (C) or by fluorescence microscopy to visualize the red chlorophyll autofluorescence of the endosymbiotic Symbiodinium algae (D).     

Redesigning photosynthesis to sustainably meet global food and bioenergy demand

The world’s crop productivity is stagnating whereas population growth, rising affluence, and mandates for biofuels put increasing demands on agriculture. Meanwhile, demand for increasing cropland competes with equally crucial global sustainability and environmental protection needs. Addressing this looming agricultural crisis will be one of our greatest scientific challenges in the coming decades, and success will require substantial improvements at many levels. We assert that increasing the efficiency and productivity of photosynthesis in crop plants will be essential if this grand challenge is to be met. Here, we explore an array of prospective redesigns of plant systems at various scales, all aimed at increasing crop yields through improved photosynthetic efficiency and performance. Prospects range from straightforward alterations, already supported by preliminary evidence of feasibility, to substantial redesigns that are currently only conceptual, but that may be enabled by new developments in synthetic biology. Although some proposed redesigns are certain to face obstacles that will require alternate routes, the efforts should lead to new discoveries and technical advances with important impacts on the global problem of crop productivity and bioenergy production.     

Gradient Spin Echo (GraSE) imaging for fast myocardial T2 mapping

Background

Quantitative Cardiovascular Magnetic Resonance (CMR) techniques have gained high interest in CMR research. Myocardial T2 mapping is thought to be helpful in diagnosis of acute myocardial conditions associated with myocardial edema. In this study we aimed to establish a technique for myocardial T2 mapping based on gradient-spin-echo (GraSE) imaging.

Methods

The local ethics committee approved this prospective study. Written informed consent was obtained from all subjects prior to CMR. A modified GraSE sequence allowing for myocardial T2 mapping in a single breath-hold per slice using ECG-triggered acquisition of a black blood multi-echo series was developed at 1.5 Tesla. Myocardial T2 relaxation time (T2-RT) was determined by maximum likelihood estimation from magnitude phased-array multi-echo data. Four GraSE sequence variants with varying number of acquired echoes and resolution were evaluated in-vitro and in 20 healthy volunteers. Inter-study reproducibility was assessed in a subset of five volunteers. The sequence with the best overall performance was further evaluated by assessment of intra- and inter-observer agreement in all volunteers, and then implemented into the clinical CMR protocol of five patients with acute myocardial injury (myocarditis, takotsubo cardiomyopathy and myocardial infarction).

Results

In-vitro studies revealed the need for well defined sequence settings to obtain accurate T2-RT measurements with GraSE. An optimized 6-echo GraSE sequence yielded an excellent agreement with the gold standard Carr-Purcell-Meiboom-Gill sequence. Global myocardial T2 relaxation times in healthy volunteers was 52.2 ± 2.0 ms (mean ± standard deviation). Mean difference between repeated examinations (n = 5) was −0.02 ms with 95% limits of agreement (LoA) of [−4.7; 4.7] ms. Intra-reader and inter-reader agreement was excellent with mean differences of −0.1 ms, 95% LoA = [−1.3; 1.2] ms and 0.1 ms, 95% LoA = [−1.5; 1.6] ms, respectively (n = 20). In patients with acute myocardial injury global myocardial T2-RTs were prolonged (mean: 61.3 ± 6.7 ms).

Conclusion

Using an optimized GraSE sequence CMR allows for robust, reliable, fast myocardial T2 mapping and quantitative tissue characterization. Clinically, the GraSE-based T2-mapping has the potential to complement qualitative CMR in patients with acute myocardial injuries.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-015-0127-z) contains supplementary material, which is available to authorized users.     

Dicer is required for chromosome segregation and gene silencing in fission yeast cells

RNA interference is a form of gene silencing in which the nuclease Dicer cleaves double-stranded RNA into small interfering RNAs. Here we report a role for Dicer in chromosome segregation of fission yeast. Deletion of the Dicer (dcr1+) gene caused slow growth, sensitivity to thiabendazole, lagging chromosomes during anaphase, and abrogated silencing of centromeric repeats. As Dicer in other species, Dcr1p degraded double-stranded RNA into approximately 23 nucleotide fragments in vitro, and dcr1Delta cells were partially rescued by expression of human Dicer, indicating evolutionarily conserved functions. Expression profiling demonstrated that dcr1+ was required for silencing of two genes containing a conserved motif.