CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis

Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies.     

Phenolic compounds in tomatoes. Natural variations and effect of gamma-irradiation

A method for determination of p-hydroxybenzaldehyde, p-coumaric acid, ferulic acid, rutin and naringenin in tomatoes based on HPLC with coulometric electrode array detection was developed. After lyophilisation and extraction the compounds were separated isocratically (acetonitrile/buffer: 14:86, v:v, or acetonitrile/buffer: 27:73, v:v, flow rate: 0.8 ml/min) on reversed phase columns (LiChrospher 60 RP select B or Spherisorb ODS2) and detected at 16 respectively 10 working electrodes set at potentials between +50 and +750 mV against palladium reference electrodes. The natural content of these components showed a strong variation between different varieties, harvests and degrees of maturity. Gamma-irradiation reduced the concentration of the phenolic compounds markedly in all tomato samples investigated, however, this change was smaller than the naturally occurring differences. The irradiation products vanillin and eriodictyol, identified in standard solutions, could not be found in irradiated tomatoes.     

Oral Treatment with RD2RD2 Impedes Development of Motoric Phenotype and Delays Symptom Onset in SOD1G93A Transgenic Mice

Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and plays a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS). It has been implicated as driver of disease progression and is observed in ALS patients, as well as in the transgenic SOD1^G93A mouse model. Here, we explore and validate the therapeutic potential of the d-enantiomeric peptide RD2RD2 upon oral administration in SOD1^G93A mice. Transgenic mice were treated daily with RD2RD2 or placebo for 10 weeks and phenotype progression was followed with several behavioural tests. At the end of the study, plasma cytokine levels and glia cell markers in brain and spinal cord were analysed. Treatment resulted in a significantly increased performance in behavioural and motor coordination tests and a decelerated neurodegenerative phenotype in RD2RD2-treated SOD1^G93A mice. Additionally, we observed retardation of the average disease onset. Treatment of SOD1^G93A mice led to significant reduction in glial cell activation and a rescue of neurons. Analysis of plasma revealed normalisation of several cytokines in samples of RD2RD2-treated SOD1^G93A mice towards the levels of non-transgenic mice. In conclusion, these findings qualify RD2RD2 to be considered for further development and testing towards a disease modifying ALS treatment.     

Dissonance and healthy weight eating disorder prevention programs: Long-term effects from a randomized efficacy trial.

Adolescent girls with body dissatisfaction (N = 481, SD = 1.4) were randomized to a dissonance-based thin-ideal internalization reduction program, healthy weight control program, expressive writing control condition, or assessment-only control condition. Dissonance participants showed significantly greater decreases in thin-ideal internalization, body dissatisfaction, negative affect, eating disorder symptoms, and psychosocial impairment and lower risk for eating pathology onset through 2- to 3-year follow-up than did assessment-only controls. Dissonance participants showed greater decreases in thin-ideal internalization, body dissatisfaction, and psychosocial impairment than did expressive writing controls. Healthy weight participants showed greater decreases in thin-ideal internalization, body dissatisfaction, negative affect, eating disorder symptoms, and psychosocial impairment; less increases in weight; and lower risk for eating pathology and obesity onset through 2- to 3-year follow-up than did assessment-only controls. Healthy weight participants showed greater decreases in thin-ideal internalization and weight than did expressive writing controls. Dissonance participants showed a 60% reduction in risk for eating pathology onset, and healthy weight participants showed a 61% reduction in risk for eating pathology onset and a 55% reduction in risk for obesity onset relative to assessment-only controls through 3-year follow-up, implying that the effects are clinically important and enduring. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Carbonic anhydrase textile structured packing for efficient CO2 absorption in methyldiethanolamine solvent

Carbonic anhydrase (CA) is an attractive biodegradable catalyst for CO₂ absorption in solvent-based CO₂ capture. However, maintaining the stability of CA as a homogeneous component of the solvents is a challenge. Solvent regeneration temperature typically exceeds the enzyme thermal tolerance, which leads to CA deactivation. To reduce the need for frequent CA replenishment and to avoid inactive CA accumulation in the solvent, this work shows the benefits of an immobilization strategy where CA is fixed in a second-generation design of textile structured packing (CATSP-2) modules. The enzyme-immobilized packing showed 1.5 times better performance in CO₂ separation compared with traditional structured packing with a corresponding increased CO₂ loading in the rich solvent. The modules exhibited good CA activity retention of ~80% during the tests without any CA replenishment. Applying CATSP-2 could potentially decrease the packing height and absorber column size for a lower cost per amount of CO₂ captured.     

Can support by digital technologies stimulate intrapreneurial behaviour? The moderating role of management support for innovation and intrapreneurial self-efficacy

Drawing on theorising on digital technologies as external enablers of entrepreneurial activities and an interactionist perspective on corporate entrepreneurship, this article examines the relationship between digital technology support and employee intrapreneurial behaviour. We propose that management support for innovation as an organisational characteristic and intrapreneurial self-efficacy as an individual characteristic moderate this relationship. Findings from a metric conjoint experiment with 1360 decisions nested within 85 employees showed that support by social media, support by collaborative technologies, and support by intelligent decision support systems were significant predictors of employee intrapreneurial behaviour. However, the relative impact of support by these digital technologies varied with different levels of management support for innovation and intrapreneurial self-efficacy.     

Polyether Cyclization Cascade Alterations in Response to Monensin Polyketide Synthase Mutations

The targeted manipulation of polyketide synthases has in recent years led to numerous new-to-nature polyketides. For type I polyketide synthases the response of post-polyketide synthases (PKS) processing enzymes onto the most frequently polyketide backbone manipulations is so far insufficiently studied. In particular, complex processes such as the polyether cyclisation in the biosynthesis of ionophores such as monensin pose interesting objects of research. We present here a study of the substrate promiscuity of the polyether cyclisation cascade enzymes in monensin biosynthesis in the conversion of redox derivatives of the nascent polyketide chain. LC-HRMS/MS²-based studies revealed a remarkable flexibility of the post-PKS enzymes. They acted on derivatized polyketide backbones based on the three possible polyketide redox states within two different modules and gave rise to an altered polyether structure. One of these monensin derivatives was isolated and characterized by 2D-NMR spectroscopy, crystallography, and bioactivity studies.