Flow of the Coarse Grained Free Energy for Crossover Phenomena

The critical behaviour of a system of two coupled scalar fields in three dimensions is studied within the formalism of the effective average action. The fixed points of the system are identified and the crossover between them is described in detail. Besides the universal critical behaviour, the flow of the coarse grained free energy also describes the approach to scaling.Comment: 18 pages, latex, 4 figures appended as uuencoded fil

Prognostic significance of the controlling nutritional status (CONUT) score in patients undergoing hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis

Background: The clinical value of the controlling nutritional status (CONUT) score in hepatocellular carcinoma (HCC) has increased. The aim of this meta-analysis was to systematically review the association between the CONUT score and outcomes in patients undergoing hepatectomy for HCC. Methods: Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar were systematically searched. Random effects meta-analyses were conducted to examine the prognostic value of the CONUT score in HCC patients. Results: A total of five studies including 4679 patients were found to be eligible and analyzed in the meta-analysis. The CONUT score was significantly associated with overall survival (HR 1.78, 95%CI = 1.20-2.64, P = 0.004, I-2 = 79%), recurrence-free survival (HR 1.34, 95%CI = 1.17-1.53, P Conclusions: The CONUT score is an independent prognostic indicator of the prognosis and is associated with postoperative major complications and hepatic functional reserve in HCC patients

Coenzyme Q10 levels are low and may be associated with the inflammatory cascade in septic shock

Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo. We conducted a post hoc analysis of a prospective, randomized trial of simvastatin versus placebo in patients with septic shock (ClinicalTrials.gov ID: NCT00676897). Adult patients with suspected or confirmed infection and the need for vasopressor support were included in the initial trial. For the current analysis, blood specimens were analyzed for plasma CoQ10 and low-density lipoprotein (LDL) levels. The relationship between CoQ10 levels and inflammatory and vascular endothelial biomarkers was assessed using either the Pearson or Spearman correlation coefficient. We analyzed 28 samples from 14 patients. CoQ10 levels were low, with a median of 0.49 (interquartile range 0.26 to 0.62) compared to levels in healthy control patients (CoQ10 = 0.95 μmol/L ± 0.29; P < 0.0001). Statin therapy had no effect on plasma CoQ10 levels over time (P = 0.13). There was a statistically significant relationship between plasma CoQ10 levels and levels of vascular cell adhesion molecule (VCAM) (r2 = 0.2; P = 0.008), TNF-α (r2 = 0.28; P = 0.004), IL-8 (r2 = 0.21; P = 0.015), IL-10 (r2 = 0.18; P = 0.025), E-selectin (r2 = 0.17; P = -0.03), IL-1ra (r2 = 0.21; P = 0.014), IL-6 (r2 = 0.17; P = 0.029) and IL-2 (r2 = 0.23; P = 0.009). After adjusting for LDL levels, there was a statistically significant inverse relationship between plasma CoQ10 levels and levels of VCAM (r2 = 0.24; P = 0.01) (Figure 3) and IL-10 (r2 = 0.24; P = 0.02). CoQ10 levels are significantly lower in septic shock patients than in healthy controls. CoQ10 is negatively associated with vascular endothelial markers and inflammatory molecules, though this association diminishes after adjusting for LDL levels

Impact of Underlying Depression on Treatment of Neuropsychiatric Symptoms in Older Adults with Dementia

This article examines the moderating effect of depression on interdisciplinary treatment approaches for behaviors in dementia. A secondary analysis of data collected on tailored treatment of 105 long-term care residents with dementia found a significant relationship between treatment and passivity (p &lt; 0.001), treatment and agitation (p = 0.001), and the mediating effect of change in passivity on change in agitation (p &lt; 0.001). The moderating effect of depression was found as a significant factor. For participants with depression and agitation, a significant change in passive behavior was related to significant change in agitated behavior. Thus, by focusing treatment on passivity, both types of neuropsychiatric behaviors improved. The implications of thoroughly assessing not only a behavior problem such as agitation but also other neuropsychiatric symptoms that complicate the delivery of the intervention are discussed

Mutations in the 3'-untranslated region of GATA4 as molecular hotspots for congenital heart disease (CHD)

<p>Abstract</p> <p>Background</p> <p>The 3'-untranslated region (3'-UTR) of mRNA contains regulatory elements that are essential for the appropriate expression of many genes. These regulatory elements are involved in the control of nuclear transport, polyadenylation status, subcellular targetting as well as rates of translation and degradation of mRNA. Indeed, 3'-UTR mutations have been associated with disease, but frequently this region is not analyzed. To gain insights into congenital heart disease (CHD), we have been analyzing cardiac-specific transcription factor genes, including <it>GATA4</it>, which encodes a zinc finger transcription factor. Germline mutations in the coding region of <it>GATA4 </it>have been associated with septation defects of the human heart, but mutations are rather rare. Previously, we identified 19 somatically-derived zinc finger mutations in diseased tissues of malformed hearts. We now continued our search in the 609 bp 3'-UTR region of <it>GATA4 </it>to explore further molecular avenues leading to CHD.</p> <p>Methods</p> <p>By direct sequencing, we analyzed the 3'-UTR of <it>GATA4 </it>in DNA isolated from 68 formalin-fixed explanted hearts with complex cardiac malformations encompassing ventricular, atrial, and atrioventricular septal defects. We also analyzed blood samples of 12 patients with CHD and 100 unrelated healthy individuals.</p> <p>Results</p> <p>We identified germline and somatic mutations in the 3'-UTR of <it>GATA4</it>. In the malformed hearts, we found nine frequently occurring sequence alterations and six dbSNPs in the 3'-UTR region of <it>GATA4</it>. Seven of these mutations are predicted to affect RNA folding. We also found further five nonsynonymous mutations in exons 6 and 7 of <it>GATA4</it>. Except for the dbSNPs, analysis of tissue distal to the septation defect failed to detect sequence variations in the same donor, thus suggesting somatic origin and mosaicism of mutations. In a family, we observed c.+119A > T in the 3'-UTR associated with ASD type II.</p> <p>Conclusion</p> <p>Our results suggest that somatic <it>GATA4 </it>mutations in the 3'-UTR may provide an additional molecular rationale for CHD.</p

The Generation of Successive Unmarked Mutations and Chromosomal Insertion of Heterologous Genes in Actinobacillus pleuropneumoniae Using Natural Transformation

We have developed a simple method of generating scarless, unmarked mutations in Actinobacillus pleuropneumoniae by exploiting the ability of this bacterium to undergo natural transformation, and with no need to introduce plasmids encoding recombinases or resolvases. This method involves two successive rounds of natural transformation using linear DNA: the first introduces a cassette carrying cat (which allows selection by chloramphenicol) and sacB (which allows counter-selection using sucrose) flanked by sequences to either side of the target gene; the second transformation utilises the flanking sequences ligated directly to each other in order to remove the cat-sacB cassette. In order to ensure efficient uptake of the target DNA during transformation, A. pleuropneumoniae uptake sequences are added into the constructs used in both rounds of transformation. This method can be used to generate multiple successive deletions and can also be used to introduce targeted point mutations or insertions of heterologous genes into the A. pleuropneumoniae chromosome for development of live attenuated vaccine strains. So far, we have applied this method to highly transformable isolates of serovars 8 (MIDG2331), which is the most prevalent in the UK, and 15 (HS143). By screening clinical isolates of other serovars, it should be possible to identify other amenable strains

Распределение взвешенных частиц в Баренцевом море в конце зимы 2019 г.

Arctic summer and winter sea-ice extent is continuously declining as a result of climate change, affecting the hydrography and biogeochemical cycles on the seasonally ice-free Eurasian Shelves. The prolongation of the open-water season causes higher sediment resuspension and coastal erosion due to larger wind fetch and wave heights. This impacts the optical properties of the water column and hence biological productivity in this region. During “Transarktika-2019” leg 1 in late winter 2019, a comprehensive dataset of filtered water samples and optical data was collected throughout the central and northern Barents Sea. Combining suspended particulate matter concentrations obtained from water samples and optical data revealed a pronounced bottom nepheloid layer on the Barents Sea shelf even under ice-covered conditions. Moreover, the data indicate that the Franz Viktoria Trough could be a major pathway for sediment transport into the Eurasian Basin. Therefore, to link changes in sediment distribution and its impact on the ecosystem under a warming climate, further studies of sediment dynamics are required, particularly during winter.Летняя и зимняя площадь ледяного покрова в Арктике постоянно сокращается в результате изменения климата, воздействуя на гидрофизические и биогеохимические циклы на сезонно-безледных шельфах Евразийского бассейна. Возрастание продолжительности периода открытой воды приводит к увеличению образования взвешенного осадка и береговой эрозии в связи с увеличением ветровой нагрузки и высоты волн. Это влияет на оптические свойства водной толщи и, следовательно, на биологическую продуктивность в этом регионе. Во время первого этапа экспедиции «Трансарктика-2019» в конце зимы 2019 г. в центральной и северной частях Баренцева моря был собран обширный объем данных взвешенных частиц из фильтрованной воды и оптических данных. Совместный анализ данных о концентрации взвешенного вещества, полученных из проб воды, и оптических данных показал наличие ярко выраженного донного нефелоидного слоя на шельфе Баренцева моря даже в условиях наличия ледяного покрова. Более того, полученные результаты свидетельствуют о том, что желоб Франц-Виктория может быть основным путем переноса осадочного материала в Евразийский бассейн. Поэтому для того, чтобы связать изменения в распределении осадочных отложений и их влияние на экосистему в условиях потепления климата, необходимы дальнейшие исследования динамики осадочных отложений, особенно в зимний период

Exponential Distribution of Locomotion Activity in Cell Cultures

In vitro velocities of several cell types have been measured using computer controlled video microscopy, which allowed to record the cells' trajectories over several days. On the basis of our large data sets we show that the locomotion activity displays a universal exponential distribution. Thus, motion resulting from complex cellular processes can be well described by an unexpected, but very simple distribution function. A simple phenomenological model based on the interaction of various cellular processes and finite ATP production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure

Intestinal Organoids in Colitis Research: Focusing on Variability and Cryopreservation

In recent years, stem cell-derived organoids have become a cell culture standard that is widely used for studying various scientific issues that were previously investigated through animal experiments and using common tumor cell lines. After their initial hype, concerns regarding their standardization have been raised. Here, we aim to provide some insights into our experience in standardizing murine colonic epithelial organoids, which we use as a replacement method for research on inflammatory bowel disease. Considering good scientific practice, we examined various factors that might challenge the design and outcome of experiments using these organoids. First, to analyze the impact of antibiotics/antimycotics, we performed kinetic experiments using ZellShield® and measured the gene expression levels of the tight junction markers Ocln, Zo-1, and Cldn4, the proliferation marker Ki67, and the proinflammatory cytokine Tnfα. Because we found no differences between cultivations with and without ZellShield®, we then performed infection experiments using the probiotic Escherichia coli Nissle 1917 as an already established model setup to analyze the impact of technical, interexperimental, and biologic replicates. We demonstrate that interexperimental differences pose the greatest challenge for reproducibility and explain our strategies for addressing these differences. Additionally, we conducted infection experiments using freshly isolated and cryopreserved/thawed organoids and found that cryopreservation influenced the experimental outcome during early passages. Formerly cryopreserved colonoids exhibited a premature appearance and a higher proinflammatory response to bacterial stimulation. Therefore, we recommend analyzing the growth characteristics and reliability of cryopreserved organoids before to their use in experiments together with conducting several independent experiments under standardized conditions. Taken together, our findings demonstrate that organoid culture, if standardized, constitutes a good tool for reducing the need for animal experiments and might further improve our understanding of, for example, the role of epithelial cells in inflammatory bowel disease development

Mechanistic investigation into the C(sp3)–H acetoxylation of morpholinones

The study of a selective palladium(II)-catalyzed C(sp3 )–H acetoxylation reaction on a class of cyclic alkyl amines is reported. Computational modelling and kinetic studies were used to provide support for a mechanism involving selective C–O bond formation from a g-aminoalkyl-Pd(IV) intermediate. The C–O bond forming step was computed to occur by a dissociative ionization mechanism followed by an SN2 process involving external acetate attack at the C–Pd(IV) bond. This pathway was computed to be of lowest energy with no competing C–N products observed. Additionally, with a few modifications to reaction conditions, preliminary studies showed that this process could be rendered enantioselective in the presence of a non-racemic BINOL-phosphoric acid