One year of exercise training promotes distinct adaptations in right and left ventricle of female Sprague-Dawley rats

Journal of Physiology and Biochemistry - Aerobic exercise training induces a unique cardioprotective phenotype, but it is becoming clear that it does not promote the same structural, functional,...     

NUMB does not impair growth and differentiation status of experimental gliomas

The cell fate determinant NUMB orchestrates asymmetric cell division in flies and mammals and has lately been suggested to have a tumor suppressor function in breast and lung cancer. Here, we studied NUMB in the context of malignant gliomas. We used ectopic expression of NUMB in order to inhibit proliferation and induce differentiation in glioma cells by alteration of Notch, Hedgehog and p53 signaling. We found that NUMB is consistently expressed in glioma biopsies with predominance of NUMB2/4 isoforms as determined by isoform-specific real-time PCR and Western blotting. Upon lentiviral overexpression, in vitro proliferation rate and the grade of differentiation as assessed by morphology and expression of neural and glial markers remained unchanged. Orthotopic xenografts of NUMB-transduced human U87 glioma cells could be established in nude rats without impairing engraftment or causing significant changes in morphology based on magnetic resonance imaging (MRI). The previously reported alteration of Hedgehog and p53 signaling by NUMB could not be recapitulated in glioma cells. We thus show that in experimental gliomas, NUMB overexpression most likely does not exert a tumor suppressor function such as seen in epithelial cancers.     

Development,morphology and ultrastructure of the branchial crown of Fabricia stellaris (Müller, 1774) (Polychaeta: Sabellida: Fabriciinae)

Randel, N. and Bick, A. 2011. Development, morphology and ultrastructure of the branchial crown of Fabricia stellaris (Müller, 1774) (Polychaeta: Sabellida: Fabriciinae). —Acta Zoologica (Stockholm) 93 : 409–421. Sabellidae and Serpulidae are well‐known tube‐building polychaetes with a distinctive and often spectacularly colourful branchial crown. Morphological investigations suggest that these taxa form the monophyletic clade Sabellida, with the adelphotaxa Sabellidae and Serpulidae, but the relationship between these taxa remains ambiguous. Molecular investigations have indicated that the Fabriciinae, major taxon of Sabellidae, belongs to Serpulidae, thereby making Sabellidae paraphyletic; however, morphological characters are absent to support this result. We investigate the development, anatomy and ultrastructure of the branchial crown of Fabricia stellaris (Müller, 1774), describing morphological characteristics useful not only for constructing morphological phylogenies but also for understanding the evolution of the branchial crown. The morphology of the radioles and pinnules does not differ from each other. The supporting tissue of the branchial crown consists of myoepithelial cells and a solid extracellular matrix (ECM). Both ciliated and non‐ciliated cells form the epidermal layer; ciliated cells shape the food groove. Most important is the result that radioles and pinnules within Sabellida may not be homologous, because the morphology and the branching of radioles and pinnules are completely different between Sabellinae, Fabriciinae and Serpulidae. The terms ‘primary branch’ for radioles and ‘secondary branch’ for pinnules are proposed for Fabriciinae. The phylogeny of the Sabellida is discussed.     

Sensitive Troponins – Which Suits Better for Hemodialysis Patients? Associated Factors and Prediction of Mortality

Background

In hemodialysis patients, elevated plasma troponin concentrations are a common finding that has even increased with the advent of newly developed sensitive assays. However, the interpretation and relevance of this is still under debate.

Methods

In this cross-sectional study, we analyzed plasma concentrations of sensitive troponin I (TnI) and troponin T (TnT) in stable ambulatory hemodialysis patients (n = 239) and investigated their associations with clinical factors and mortality.

Results

In all of the enrolled patients, plasma TnI or TnT was detectable at a median concentration of 14 pg/ml (interquartile range: 7–29) using the Siemens TnI ultra assay and 49 pg/ml (31–74) using the Roche Elecsys high sensitive TnT assay. Markedly more patients exceeded the 99th percentile for TnT than for TnI (95% vs. 14%, p<0.0001). In a multivariate linear regression model, TnT was independently associated with age, gender, systolic dysfunction, time on dialysis, residual diuresis and systolic blood pressure, whereas TnI was independently associated with age, systolic dysfunction, pulse pressure, time on dialysis and duration of a HD session. During a follow-up period of nearly two years, TnT concentration above 38 pg/mL was associated with a 5-fold risk of death, whereas elevation of TnI had a gradual association to mortality.

Conclusion

In hemodialysis patients, elevations of plasma troponin concentrations are explained by cardiac function and dialysis-related parameters, which contribute to cardiac strain. Both are highly predictive of increased risk of death.     

Impact of miR-21, miR-126 and miR-221 as Prognostic Factors of Clear Cell Renal Cell Carcinoma with Tumor Thrombus of the Inferior Vena Cava

Clear cell renal cell carcinoma (ccRCC) characterized by a tumor thrombus (TT) extending into the inferior vena cava (IVC) generally indicates poor prognosis. Nevertheless, the risk for tumor recurrence after nephrectomy and thrombectomy varies. An applicable and accurate prediction system to select ccRCC patients with TT of the IVC (ccRCC/TT) at high risk after nephrectomy is urgently needed, but has not been established up to now. To our knowledge, a possible role of microRNAs (miRs) for the development of ccRCC/TT or their impact as prognostic markers in ccRCC/TT has not been explored yet. Therefore, we analyzed the expression of the previously described onco-miRs miR-200c, miR-210, miR-126, miR-221, let-7b, miR-21, miR-143 and miR-141 in a study collective of 74 ccRCC patients. Using the expression profiles of these eight miRs we developed classification systems that accurately differentiate ccRCC from non-cancerous renal tissue and ccRCC/TT from tumors without TT. In the subgroup of 37 ccRCC/TT cases we found that miR-21, miR-126, and miR-221 predicted cancer related death (CRD) accurately and independently from other clinico-pathological features. Furthermore, a combined risk score based on the expression of miR-21, miR-126 and miR-221 was developed and showed high sensitivity and specificity to predict cancer specific survival (CSS) in ccRCC/TT. Using the combined risk score we were able to classify ccRCC/TT patients correctly into high and low risk cases. The risk stratification by the combined risk score (CRS) will benefit from further cohort validation and might have potential for clinical application as a molecular prediction system to identify high- risk ccRCC/TT patients.     

Natural climate solutions versus bioenergy: Can carbon benefits of natural succession compete with bioenergy from short rotation coppice?

Short rotation plantations are often considered as holding vast potentials for future global bioenergy supply. In contrast to raising biomass harvests in forests, purpose‐grown biomass does not interfere with forest carbon (C) stocks. Provided that agricultural land can be diverted from food and feed production without impairing food security, energy plantations on current agricultural land appear as a beneficial option in terms of renewable, climate‐friendly energy supply. However, instead of supporting energy plantations, land could also be devoted to natural succession. It then acts as a long‐term C sink which also results in C benefits. We here compare the sink strength of natural succession on arable land with the C saving effects of bioenergy from plantations. Using geographically explicit data on global cropland distribution among climate and ecological zones, regionally specific C accumulation rates are calculated with IPCC default methods and values. C savings from bioenergy are given for a range of displacement factors (DFs), acknowledging the varying efficiency of bioenergy routes and technologies in fossil fuel displacement. A uniform spatial pattern is assumed for succession and bioenergy plantations, and the considered timeframes range from 20 to 100 years. For many parameter settings—in particular, longer timeframes and high DFs—bioenergy yields higher cumulative C savings than natural succession. Still, if woody biomass displaces liquid transport fuels or natural gas‐based electricity generation, natural succession is competitive or even superior for timeframes of 20–50 years. This finding has strong implications with climate and environmental policies: Freeing land for natural succession is a worthwhile low‐cost natural climate solution that has many co‐benefits for biodiversity and other ecosystem services. A considerable risk, however, is C stock losses (i.e., emissions) due to disturbances or land conversion at a later time.     

Direct Observation of Surface Plasmon Polariton Propagation and Interference by Time-Resolved Imaging in Normal-Incidence Two Photon Photoemission Microscopy

Plasmonics - Time-resolved imaging of the propagation and interference of isolated ultrashort surface plasmon polariton wave packets is demonstrated using two photon photoemission microscopy. The...     

Goblet Cell Carcinoids: Characteristics of a Danish Cohort of 83 Patients

BackgroundAppendiceal goblet cell carcinoids (GCCs) exhibit neuroendocrine and adenocarcinoma features.ResultsMedian age for f/m was 59/58 years, respectively, and similar for localized and disseminated disease. At diagnosis 54 patients had localized appendiceal disease (f/m: 29/25). According to TNM 24% had Stage I, 70% had Stage II and 6% had Stage III. Twenty-nine patients had disseminated disease (f/m: 27/2). Chromogranin A, synaptophysin and p53 were positive in >90%. Serotonin was positive in 70%. Median Ki67 index was 32% (6-75%) and higher in Tang group C (50%) compared to group A (30%; p<0.0001), and group B (30%; p<0.004). All patients had surgery. Sixty-three (76%) had radical resections including all patients with localized disease. Median OS was 83 months. The 1-, 5- and 10-year survival rates were 90%, 58%, and 38%, respectively. For localized disease OS was 164 months and 1-, 5- and 10-year survival rates were 100%, 80%, and 55%, respectively. For disseminated disease OS was 19 months and 1-, 5- and 10-year survival rates were 73%, 18% and 6%, respectively. The 1-, 5- and 10 year-survival rates for f/m were 87%/96%, 49%/76% and 31%/57%, respectively (p = 0.02). According to the Tang classification group A, B, and C OS was 118, 83 and 20 months, respectively (p = 0.0002).ConclusionThe Tang classification was found to be a significant prognostic factor, while the Ki67 index was not. Localized GCCs occurred equally in males and females, while disseminated GCCs were mostly seen in females. Median age of patients with localized disease and disseminated disease was identical. Cox regression analysis found Stage IV, focally positive synaptophysin and non-radical surgery as strongest negative prognostic factors.     

The EF-Hand Ca2+ Binding Protein MICU Choreographs Mitochondrial Ca2+ Dynamics in Arabidopsis

Plant organelle function must constantly adjust to environmental conditions, which requires dynamic coordination. Ca²⁺ signaling may play a central role in this process. Free Ca²⁺ dynamics are tightly regulated and differ markedly between the cytosol, plastid stroma, and mitochondrial matrix. The mechanistic basis of compartment-specific Ca²⁺ dynamics is poorly understood. Here, we studied the function of At-MICU, an EF-hand protein of Arabidopsis thaliana with homology to constituents of the mitochondrial Ca²⁺ uniporter machinery in mammals. MICU binds Ca²⁺ and localizes to the mitochondria in Arabidopsis. In vivo imaging of roots expressing a genetically encoded Ca²⁺ sensor in the mitochondrial matrix revealed that lack of MICU increased resting concentrations of free Ca²⁺ in the matrix. Furthermore, Ca²⁺ elevations triggered by auxin and extracellular ATP occurred more rapidly and reached higher maximal concentrations in the mitochondria of micu mutants, whereas cytosolic Ca²⁺ signatures remained unchanged. These findings support the idea that a conserved uniporter system, with composition and regulation distinct from the mammalian machinery, mediates mitochondrial Ca²⁺ uptake in plants under in vivo conditions. They further suggest that MICU acts as a throttle that controls Ca²⁺ uptake by moderating influx, thereby shaping Ca²⁺ signatures in the matrix and preserving mitochondrial homeostasis. Our results open the door to genetic dissection of mitochondrial Ca²⁺ signaling in plants.