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Silicosis : geographic changes in research ; an analysis employing density-equalizing mapping
(2014)
Background: A critical evaluation of scientific efforts is needed in times of modified evaluation criteria for academic personnel and institutions.
Methods: Using scientometric benchmark procedures and density-equalizing mapping, we analysed the global scientific efforts on "silicosis" of the last 92 years focusing on geographical changes within the last 30 years, specifying the most productive authors, institutions, countries and the most successful cooperations.
Results: The USA as the most productive supplier have established their position as center of international cooperation, followed in considerable distance by the United Kingdom, Germany and China. Asian countries, particularly China, catch up and are expected to excel the USA still in this decade.
Conclusion: The combination of scientometric procedures with density-equalizing mapping reveals a distinct global pattern of research productivity and citation activity. Modified h-index, citationrate and impact factor have to be discussed critically due to distortion by bias of self-citation, language and co-authorship.
Water footprints have been proposed as sustainability indicators, relating the consumption of goods like food to the amount of water necessary for their production and the impacts of that water use in the source regions. We further developed the existing water footprint methodology, by globally resolving virtual water flows from production to consumption regions for major food crops at 5 arcmin spatial resolution. We distinguished domestic and international flows, and assessed local impacts of export production. Applying this method to three exemplary cities, Berlin, Delhi and Lagos, we find major differences in amounts, composition, and origin of green and blue virtual water imports, due to differences in diets, trade integration and crop water productivities in the source regions. While almost all of Delhi's and Lagos' virtual water imports are of domestic origin, Berlin on average imports from more than 4000 km distance, in particular soy (livestock feed), coffee and cocoa. While 42% of Delhi's virtual water imports are blue water based, the fractions for Berlin and Lagos are 2 and 0.5%, respectively, roughly equal to the water volumes abstracted in these two cities for domestic water use. Some of the external source regions of Berlin's virtual water imports appear to be critically water scarce and/or food insecure. However, for deriving recommendations on sustainable consumption and trade, further analysis of context-specific costs and benefits associated with export production will be required.
Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by problems in social behaviour, which are sometimes similar to some symptoms of autism-spectrum disorders (ASD). However, neuronal mechanisms of ASD-like deficits in ADHD have rarely been studied. The processing of biological motion–recently discussed as a marker of social cognition–was found to be disrupted in ASD in several studies. Thus in the present study we tested if biological motion processing is disrupted in ADHD. We used 64-channel EEG and spatio-temporal source analysis to assess event-related potentials associated with human motion processing in 21 children and adolescents with ADHD and 21 matched typically developing controls. On the behavioural level, all subjects were able to differentiate between human and scrambled motion. But in response to both scrambled and biological motion, the N200 amplitude was decreased in subjects with ADHD. After a spatio-temporal dipole analysis, a human motion specific activation was observable in occipital-temporal regions with a reduced and more diffuse activation in ADHD subjects. These results point towards neuronal determined alterations in the processing of biological motion in ADHD.
Over the past decade, Scandinavian and German scholars have been active in the redefinition of the terms “Vitalism” and “Vitalist” as descriptive categories for analytical purposes in the fields of literary and cultural history. In this context,“Vitalism”has primarily been used to describe an enthusiastic worshipping of life, one that holds youth, health, strength and beauty as its primary attributes, which was prevalent in all aspects of cultural life around 1900. But even the post war founders of the Vitalist re-conceptualisation of this era, Wolfdietrich Rasch and Gunter Martens, warned of taking such a unilateral view ofwhat constituted a Vitalist concept of life. It could lead to a misunderstanding of Vitalist way of thinking, Rasch said, if the focus wasonly set upon the enthusiastic surplus, the worshipping of youth and health. To Vitalists, life is more than that. It is a totality that also encompasses notions of destruction, decay and death. “All life symbols in literature around 1900 are at the same time symbols of death” (Rasch, 1967:24).Through the analyses of three poems, this article aims to show concrete examples of how cyclic Vitalist thinking is embedded in poetry of the era. The analyses include a further sub-categorisation to capture the different types of Life Force dealt with in the texts. By way of an introduction, Vitalism is discussed within the context of the scientific and social developments of the 19th Century.
Treating large bone defects represents a major challenge in traumatic and orthopedic surgery. Bone tissue engineering provides a promising therapeutic option to improve the local bone healing response. In the present study tissue biocompatibility, systemic toxicity and tumorigenicity of a newly developed composite material consisting of polylactic acid (PLA) and 20% or 40% bioglass (BG20 and BG40), respectively, were analyzed. These materials were seeded with mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) and tested in a rat calvarial critical size defect model for 3 months and compared to a scaffold consisting only of PLA. Serum was analyzed for organ damage markers such as GOT and creatinine. Leukocyte count, temperature and free radical indicators were measured to determine the degree of systemic inflammation. Possible tumor occurrence was assessed macroscopically and histologically in slides of liver, kidney and spleen. Furthermore, the concentrations of serum malondialdehyde (MDA) and sodium oxide dismutase (SOD) were assessed as indicators of tumor progression. Qualitative tissue response towards the implants and new bone mass formation was histologically investigated. BG20 and BG40, with or without progenitor cells, did not cause organ damage, long-term systemic inflammatory reactions or tumor formation. BG20 and BG40 supported bone formation, which was further enhanced in the presence of EPCs and MSCs.
This investigation reflects good biocompatibility of the biomaterials BG20 and BG40 and provides evidence that additionally seeding EPCs and MSCs onto the scaffold does not induce tumor formation.
Lichens are present in most land ecosystems, frequently occupying habitats where few other organisms are able to survive. Their contribution to the ecosystems in terms of biomass and ground cover increases with latitude and altitude, being, together with bryophytes, the most conspicuous component of alpine and polar landscapes. Whereas some polar lichens have reduced distributions and are restricted to high latitudes, most of them have very wide distributional ranges, which oven extend over several climatic regions. Many of them are common to Polar Regions of both hemispheres, a distributional pattern that has been denominated as bipolar, antitropical or amphitropical. Bipolar distributions are not exclusive to lichens, but common to many groups of organisms. The bipolar element in lichens is exceptional as it includes a large number of species, while in most other land organisms it includes genera or families but very seldom species.
In this dissertation I use the bipolar lichen Cetraria aculeata to give a first insight into the phylogeography of this biogeographic element in lichens. I discuss how and when the disjunct distribution of C. aculeata came to be, and try to partial out the roles that historical and ecological processes played in shaping its distribution.
Sampling was designed to cover a wide geographic extension. The main e"ort was made to collect in boreal, temperate and tropical mountain ranges in North and South America, as well to include Mediterranean populations in which specimens with deviant morphologies are observed.
I found that Cetraria aculeata forms a genetically congruent taxon. Although whether it should include C. muricata remains unsolved, I excluded all specimens identified as the latter from our analyses. Thee populations of both algal and fungal symbionts have a strong geographic structure. The study of the lichen fungus suggested that the species originated in the Eurasian continent and later expanded to acquire its current distribution during the Pleistocene. The results showed that all American populations originated from an ancestral population, more similar to the extant Arctic populations than to the Mediterranean ones.
The comparison between the structure of fungal and algal populations showed a high degree of coherence between them. However, the similarity in photobiont use between Arctic and Antarctic populations suggests that photobiont use responds not only to a history of codispersal in vegetative propagula, but it is also a result of a selective process related to climate. Since this climatic pattern of similarity is also found in the community of Alphaproteobacteria associated with C. aculeata, we concluded that lichens might be able to accommodate or to respond to different environmental conditions by selectively associating with different symbiotic partners.
Lastly, we found the Mediterranean populations of C. aculeata to be genetically differentiated in algal and fungal symbionts from the rest of the populations. While we found no grounds to believe that the overgrown morphs encountered in the region are due to the association with different algal lineages, I believe that a switch in photobiont use might be responsible for the pattern of genetic isolation encountered. Furthermore, I suggest that the Mediterranean and bipolar C. aculeata could be two different species, since both are ecologically, genetically and at least in part morphologically divergent.
Conjugated vaccines consisting of flagellin and antigen activate TLR5 and induce strong innate and adaptive immune responses. Objective of the present study was to gain further insight into the mechanisms by which flagellin fusion proteins mediate their immune modulating effects. In a mouse model of Ova-induced intestinal allergy a fusion protein of flagellin and Ova (rflaA:Ova) was used for intranasal and intraperitoneal vaccination. Aggregation status of flaA, Ova and flaA:Ova were compared by light scattering, uptake of fluorescence labeled proteins into mDC was analyzed, processing was investigated by microsomal digestion experiments. Mechanism of DC-activation was investigated using proteasome and inflammasome inhibitors. Immune responses of wildtype, IL-10−/−, TLR5−/− mDCs and Ova-transgenic T cells were investigated. Mucosal and i.p.-application of rflaA:Ova were able to prevent allergic sensitization, suppress disease-related symptoms, prevent body weight loss and reduction in food uptake. Intranasal vaccination resulted in strongest suppression of Ova-specific IgE production. These protective effects were associated with increased aggregation of rflaA:Ova and accompanied by tenfold higher uptake rates into mDC compared to the mixture of both proteins. Microsomal digestion showed that stimulation with rflaA:Ova resulted in faster degradation and the generation of different peptides compared to rOva. rflaA:Ova-mediated activation of mDC could be suppressed in a dose-dependent manner by the application of both inflammasome and proteasome inhibitors. Using TLR5−/− mDC the rflaA:Ova induced IL-10 secretion was shown to be TLR5 dependent. In co-cultures of IL-10−/− mDC with DO11.10 T cells the lack of rflaA:Ova-mediated IL-10 secretion resulted in enhanced levels of both TH2 (IL-4, IL-5) and TH1 (IL-2 and IFN-y) cytokines. In summary, mucosal vaccination with flaA:Ova showed strongest preventive effect. Stimulation with rflaA:Ova results in strong immune modulation mediated by enhanced uptake of the aggregated fusion protein, likely resulting in a different processing by DC as well as stronger TLR5 mediated cell activation.
Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed.
Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-α and ribavirin for 24–72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome.
Results: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) % of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002–1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975–0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000–1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073–2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271–4.695, P = 0.007) constituted the strongest predictors of treatment response.
Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.
The taxon Syndermata comprises the biologically interesting wheel animals (“Rotifera”: Bdelloidea + Monogononta + Seisonidea) and thorny-headed worms (Acanthocephala), and is central for testing superordinate phylogenetic hypotheses (Platyzoa, Gnathifera) in the metazoan tree of life. Recent analyses of syndermatan phylogeny suggested paraphyly of Eurotatoria (free-living bdelloids and monogononts) with respect to endoparasitic acanthocephalans. Data of epizoic seisonids, however, were absent, which may have affected the branching order within the syndermatan clade. Moreover, the position of Seisonidea within Syndermata should help in understanding the evolution of acanthocephalan endoparasitism. Here, we report the first phylogenomic analysis that includes all four higher-ranked groups of Syndermata. The analyzed data sets comprise new transcriptome data for Seison spec. (Seisonidea), Brachionus manjavacas (Monogononta), Adineta vaga (Bdelloidea), and Paratenuisentis ambiguus (Acanthocephala). Maximum likelihood and Bayesian trees for a total of 19 metazoan species were reconstructed from up to 410 functionally diverse proteins. The results unanimously place Monogononta basally within Syndermata, and Bdelloidea appear as the sister group to a clade comprising epizoic Seisonidea and endoparasitic Acanthocephala. Our results support monophyly of Syndermata, Hemirotifera (Bdelloidea + Seisonidea + Acanthocephala), and Pararotatoria (Seisonidea + Acanthocephala), rejecting monophyly of traditional Rotifera and Eurotatoria. This serves as an indication that early acanthocephalans lived epizoically or as ectoparasites on arthropods, before their complex lifecycle with arthropod intermediate and vertebrate definite hosts evolved.
miRNA let-7e is involved in stem cell differentiation, and metalloproteinases are among its potential target genes. We hypothesized that the inhibitory action of let-7e on regulation of MMP9 expression could represent a crucial mechanism during differentiation of adipose-derived stem cells (ASCs). ASCs were differentiated with all-trans retinoic acid (ATRA) to promote differentiation, and the effect of let-7 silencing during differentiation was tested. Results indicate that ASCs cultured with ATRA differentiated into cells of the epithelial lineage. We found that ASCs cultured with ATRA or transfected with miRNA let-7e expressed epithelial markers such as cytokeratin-18 and early renal organogenesis markers such as Pax2, Wt1, Wnt4 and megalin. Conversely, the specific knockdown of miRNA let-7e in ASCs significantly decreased the expression of these genes, indicating its vital role during the differentiation process. Using luciferase reporter assays, we also showed that MMP9 is a direct target of miRNA let-7e. Thus, our results suggest that miRNA let-7e acts as a matrix metalloproteinase-9 (MMP9) inhibitor and differentiation inducer in ASCs.
Reconstructing the early Paleogene climate dynamics of terrestrial settings in the high southern latitudes is important to assess the role of high-latitude physical and biogeochemical processes in the global climate system. However, whereas a number of high-quality Paleogene climate records has become available for the marine realm of the high southern latitudes over the recent past, the long-term evolution of coeval terrestrial climates and ecosystems is yet poorly known. We here explore the climate and vegetation dynamics on Tasmania from the middle Paleocene to the early Eocene (60.7–54.2 Ma) based on a sporomorph record from Ocean Drilling Program (ODP) Site 1172 on the East Tasman Plateau. Our results show that three distinctly different vegetation types thrived on Tasmania under a high-precipitation regime during the middle Paleocene to early Eocene, with each type representing different temperature conditions: (i) warm-temperate forests dominated by gymnosperms that were dominant during the middle and late Paleocene; (ii) cool-temperate forests dominated by southern beech (Nothofagus) and araucarians across the middle/late Paleocene transition interval (~59.5 to ~59.0 Ma); and (iii) paratropical forests rich in ferns that were established during and in the wake of the Paleocene–Eocene Thermal Maximum (PETM). The transient establishment of cool-temperate forests lacking any frost-sensitive elements (i.e., palms and cycads) across the middle/late Paleocene transition interval indicates markedly cooler conditions, with the occurrence of frosts in winter, on Tasmania during that time. The integration of our sporomorph data with previously published TEX86-based sea-surface temperatures from ODP Site 1172 documents that the vegetation dynamics on Tasmania were closely linked with the temperature evolution in the Tasman sector of the Southwest Pacific region. Moreover, the comparison of our season-specific climate estimates for the sporomorph assemblages from ODP Site 1172 with the TEX86L- and TEX86H-based temperature data suggests a warm-season bias of both calibrations for the early Paleogene of the high southern latitudes.
Background: Right heart failure is a fatal consequence of chronic pulmonary hypertension (PH). The development of PH is characterized by increased proliferation of vascular cells, in particular pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells. In the course of PH, an escalated right ventricular (RV) afterload occurs, which leads to increased perioperative morbidity and mortality. BKCa channels are ubiquitously expressed in vascular smooth muscle cells and their opening induces cell membrane hyperpolarization followed by vasodilation. Moreover, BK activation induces anti-proliferative effects in a multitude of cell types. On this basis, we hypothesized that treatment with the nebulized BK channel opener NS1619 might be a therapy option for pulmonary hypertension and tested this in rats.
Methods: (1) Rats received monocrotaline injection for PH induction. Twenty-four days later, rats were anesthetized and NS1619 or the solvent was administered by inhalation. Systemic hemodynamic parameters, RV hemodynamic parameters, and blood gas analyses were measured before as well as 30 and 120 minutes after inhalation. (2) Rat PASMCs were stimulated with PDGF-BB in the presence and absence of NS1619. AKT, ERK1 and ERK2 activation were investigated by western blot analyses, and relative cell number was determined 48 hours after stimulation.
Results: Inhalation of a 12 µM and 100 µM NS1619 solution significantly reduced RV pressure without affecting systemic arterial pressure. Blood gas analyses demonstrated significantly reduced carbon dioxide and improved oxygenation in NS1619-treated animals pointing towards a considerable pulmonary shunt-reducing effect. In PASMC’s, NS1619 (100 µM) significantly attenuated PASMC proliferation by a pathway independent of AKT and ERK1/2 activation.
Conclusion: NS1619 inhalation reduces RV pressure and improves oxygen supply and its application inhibits PASMC proliferation in vitro. Hence, BK opening might be a novel option for the treatment of pulmonary hypertension.
Recently a considerable amount of effort has been put into quantifying how interactions of the carbon and nitrogen cycle affect future terrestrial carbon sinks. Dynamic vegetation models, representing the nitrogen cycle with varying degree of complexity, have shown diverging constraints of nitrogen dynamics on future carbon sequestration. In this study, we use the dynamic vegetation model LPJ-GUESS to evaluate how population dynamics and resource competition between plant functional types, combined with nitrogen dynamics, have influenced the terrestrial carbon storage in the past and to investigate how terrestrial carbon and nitrogen dynamics might change in the future (1850 to 2100; one exemplary "business-as-usual" climate scenario). Single factor model experiments of CO2 fertilisation and climate change show generally similar directions of the responses of C–N interactions, compared to the C-only version of the model, as documented in previous studies. Under a RCP 8.5 scenario, nitrogen limitation suppresses potential CO2 fertilisation, reducing the cumulative net ecosystem carbon uptake between 1850 and 2100 by 61%, and soil warming-induced increase in nitrogen mineralisation reduces terrestrial carbon loss by 31%. When environmental changes are considered conjointly, carbon sequestration is limited by nitrogen dynamics until present. However, during the 21st century nitrogen dynamics induce a net increase in carbon sequestration, resulting in an overall larger carbon uptake of 17% over the full period. This contradicts earlier model results that showed an 8 to 37% decrease in carbon uptake, questioning the often stated assumption that projections of future terrestrial C dynamics from C-only models are too optimistic.
These are exciting times for translational medicine as the convergence between fundamental and clinical research comes of age. The new EMBO Press publishing platform reinforces the standing of EMBO Molecular Medicine as the journal that matches high quality, novel research with rigorous editorial and ethical standards. It will also cement the journal's global reach and relevance - whether in highly active fields or explorative forays into emerging areas.
Objective: Videolaryngoscopy has mainly been developed to facilitate difficult airway intubation. However, there is a lack of studies demonstrating this method's efficacy in pediatric patients. The aim of the present study was to compare the TruView infant EVO2 and the C-MAC videolaryngoscope with conventional direct Macintosh laryngoscopy in children with a bodyweight ≤10 kg in terms of intubation conditions and the time to intubation.
Methods: In total, 65 children with a bodyweight ≤10 kg (0-22 months) who had undergone elective surgery requiring endotracheal intubation were retrospectively analyzed. Our database was screened for intubations with the TruView infant EVO2, the C-MAC videolaryngoscope, and conventional direct Macintosh laryngoscopy. The intubation conditions, the time to intubation, and the oxygen saturation before and after intubation were monitored, and demographic data were recorded. Only children with a bodyweight ≤10 kg were included in the analysis.
Results: A total of 23 children were intubated using the C-MAC videolaryngoscope, and 22 children were intubated using the TruView EVO2. Additionally, 20 children were intubated using a standard Macintosh blade. The time required for tracheal intubation was significantly longer using the TruView EVO2 (52 sec vs. 28 sec for C-MAC vs. 26 sec for direct LG). However, no significant difference in oxygen saturation was found after intubation.
Conclusion: All devices allowed excellent visualization of the vocal cords, but the time to intubation was prolonged when the TruView EVO2 was used. The absence of a decline in oxygen saturation may be due to apneic oxygenation via the TruView scope and may provide a margin of safety. In sum, the use of the TruView by a well-trained anesthetist may be an alternative for difficult airway management in pediatric patients.
Objectives: This 52-week, randomised, double-blind phase IIIb study assessed efficacy and safety of certolizumab pegol (CZP) as add-on therapy to non-biologic disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients with low to moderate disease activity, and stopping therapy in patients in sustained remission.
Methods: Patients were randomised 1:1 to CZP (400 mg at weeks 0, 2 and 4, then 200 mg every 2 weeks) or placebo (every 2 weeks) plus current non-biologic DMARDs. At week 24, patients who achieved the primary endpoint of Clinical Disease Activity Index (CDAI) remission at both weeks 20 and 24 stopped study treatment and continued in the study until week 52.
Results: Of 194 patients (CZP=96; placebo=98), >90% had moderate disease activity at baseline. Significantly more CZP patients met the primary endpoint than placebo patients (week 20 and 24 CDAI remission rates: 18.8% vs 6.1%; p≤0.05). At week 24, 63.0% vs 29.7% of CZP versus placebo patients (p<0.001) achieved LDA. Disease activity score (ESR) based on 28-joint count and Simplified Disease Activity Index remission rates were also significantly higher with CZP versus placebo (19.8% vs 3.1%; p≤0.01 and 14.6% vs 4.1%; p≤0.05). CZP patients reported improvements in physical function versus placebo (mean Health Assessment Questionnaire-Disability-Index change from baseline: CZP, -0.25 vs placebo, -0.03; p≤0.01). During the period following withdrawal of CZP or placebo, only 3/17 prior CZP patients and 2/6 prior placebo patients maintained CDAI remission until week 52, but CZP reinstitution allowed renewed improvement. Adverse and serious adverse event rates were comparable between CZP and placebo groups.
Conclusions: Addition of CZP to non-biologic DMARDs is an effective treatment in RA patients with predominantly moderate disease activity, allowing low-disease activity or remission to be reached in a majority of the patients. However, the data suggest that CZP cannot be withdrawn in patients achieving remission.
We examined substrate-induced conformational changes in MjNhaP1, an archaeal electroneutral Na+/H+-antiporter resembling the human antiporter NHE1, by electron crystallography of 2D crystals in a range of physiological pH and Na+ conditions. In the absence of sodium, changes in pH had no major effect. By contrast, changes in Na+ concentration caused a marked conformational change that was largely pH-independent. Crystallographically determined, apparent dissociation constants indicated ∼10-fold stronger Na+ binding at pH 8 than at pH 4, consistent with substrate competition for a common ion-binding site. Projection difference maps indicated helix movements by about 2 Å in the 6-helix bundle region of MjNhaP1 that is thought to contain the ion translocation site. We propose that these movements convert the antiporter from the proton-bound, outward-open state to the Na+-bound, inward-open state. Oscillation between the two states would result in rapid Na+/H+ antiport.
Objective: Acute kidney injury (AKI) after cardiac surgery procedures is associated with poor patient outcomes. Cystatin C as a marker for renal failure has been shown to be of prognostic value; however, a wide range of its predictive accuracy has been reported. The aim of the study was to evaluate whether the measurement of pre- and postoperative serum cystatin C improves the prediction of AKI.
Methods: In a single-centre, prospective study of 70 patients (74 ± 9ys; range 47-85ys; 77% male), cystatin C was measured six times: (T1 = preoperative, T2 = start cardiopulmonary bypass (CPB), T3 = 20 min after CPB, T4 = end of operation; T5 = 24 h postoperatively; T6 = 7d postoperatively). Predictive property, in terms of the need for renal replacement therapy (RRT), was analysed by receiver operating characteristics (ROC) statistics and described by the area under the curve (AUC).
Results: With respect to RRT (n = 8), serum cystatin C was significantly higher at the end of the operation (T4), 24 h postoperatively at T5 and at T6. The AUCs for preoperative T1 and intraoperative T2/3 cystatin C were <0.7 (95% CI, 0.47-0.85). The earliest significant predictive AUCs were found at the end of the operation (T4: p = 0.03 95% CI 0.58-0.88 AUC 0.73) and 24 h postoperatively (T5: p = 0.003 95% CI 0.74-0.96 AUC 0.85).
Conclusions: Early postoperative serum cystatin C increase appears to be a moderate biomarker in the prediction of AKI, whereas a preoperative and intraoperative cystatin C increase has only a limited diagnostic and predictive value.
Introduction: Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated.
Methods: Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively.
Results: MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability.
Conclusions: These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.