THE COMPOSITION AND PHYLOGENETIC SIGNIFICANCE OF THE MOUGEOTIA (CHAROPHYCEAE) CELL WALL1

The two-layered, fibrillar cell wall of Mougeotia C. Agardh sp. consisted of 63.6% non-cellulosic carbohydrates and 13.4% cellulose. The orientation of cellulose microfibrils in the native cell wall agrees with the multinet growth hypothesis, which has been employed to explain the shift in microfibril orientation from transverse (inner wall) toward axial (outer wall). Monosaccharide analysis of isolated cell walls revealed the presence of ten sugars with glucose, xylose and galactose most abundant. Methylation analysis of the acid-modified, 1 N NaOH insoluble residue fraction showed that it was composed almost exclusively of 4-linked glucose, confirming the presence of cellulose. The major hemicellulosic carbohydrate was semi-purified by DEAE Sephacel (Cl^?) anion-exchange chromatography of the hot 1 N NaOH soluble fraction. This hemicellulose was a xylan consisting of a 4-xylosyl backbone and 2,4-xylosyl branch points. The major hot water soluble neutral polysaccharide was identified as a 3-linked galactan. Mougeotia cell wall composition is similar to that of (Charophyceae) and has homologies with vascular plant cell walls. Our observations support transtructural evidence which suggests that members of the Charophyceae represent the phylogenetic line that gave rise to vascular plants. Therefore, the primary cell walls of vascular plants many have evolved directly from structures typical of the filamentous green algal cell walls found in the Charophyceae.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue

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Highlights? TBLR1 controls cAMP-dependent lipolysis in adipocytes ? Adipocyte-specific deletion of TBLR1 in mice impairs fasting-induced lipolysis ? Lack of TBLR1 in adipocytes aggravates diet-induced obesity and metabolic dysfunction ? TBLR1 mRNA levels in WAT are elevated under lipolytic conditions in mice and humans     

Iron Regulatory Proteins Control a Mucosal Block to Intestinal Iron Absorption

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Highlights? Disruption of intestinal IRP function constrains iron absorption in adult mice ? IRPs must limit mucosal ferritin for efficient iron absorption ? IRPs control ferroportin directly and DMT1 directly or through HIF2α ? IRPs define a set point for hepcidin-mediated regulation of iron absorption     

Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

Background and Purpose

In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.

Materials and Method

In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression.

Results

Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.

Conclusions

Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method.     

Identification of liver‐derived bone morphogenetic protein (BMP)‐9 as a potential new candidate for treatment of colorectal cancer

Colorectal cancer (CRC) is a high‐incidence malignancy worldwide which still needs better therapy options. Therefore, the aim of the present study was to investigate the responses of normal or malignant human intestinal epithelium to bone morphogenetic protein (BMP)‐9 and to find out whether the application of BMP‐9 to patients with CRC or the enhancement of its synthesis in the liver could be useful strategies for new therapy approaches. In silico analyses of CRC patient cohorts (TCGA database) revealed that high expression of the BMP‐target gene ID1, especially in combination with low expression of the BMP‐inhibitor noggin, is significantly associated with better patient survival. Organoid lines were generated from human biopsies of colon cancer (T‐Orgs) and corresponding non‐malignant areas (N‐Orgs) of three patients. The N‐Orgs represented tumours belonging to three different consensus molecular subtypes (CMS) of CRC. Overall, BMP‐9 stimulation of organoids promoted an enrichment of tumour‐suppressive gene expression signatures, whereas the stimulation with noggin had the opposite effects. Furthermore, treatment of organoids with BMP‐9 induced ID1 expression (independently of high noggin levels), while treatment with noggin reduced ID1.In summary, our data identify the ratio between ID1 and noggin as a new prognostic value for CRC patient outcome. We further show that by inducing ID1, BMP‐9 enhances this ratio, even in the presence of noggin. Thus, BMP‐9 is identified as a novel target for the development of improved anti‐cancer therapies of patients with CRC.     

A new in vitro bioassay for cyst formation by renal cells from an autosomal dominant rat model of polycystic kidney disease

Summary Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent human inherited diseases. The main feature of the disease is the development of renal cysts, first occurring in the proximal tubules, and with time, dominating all segments of the nephron, leading to end-stage renal disease in 50% of the patients in their fifth decade of life. A therapy for polycystic kidney disease (PKD) has not yet been developed. Patients coming to end-stage ADPKD require long-term dialysis and/or transplantation. A suitable animal model to study ADPKD is the spontaneously mutated Han:SPRD (cy/ +) rat, but a method to cultivate Han:SPRD (cy/ +) derived renal cells which preserves their ability to form cyst-like structures in vitro has previously not been reported. Based on this well-characterized animal model, we developed a cell culture model of renal cyst formation in vitro. When renal cells of the Han:SPRD (cy/ +) rat were isolated and cultured under conditions that prevent cell-substratum adhesion, large amounts of cyst-like structures were formed de novo from Han:SPRD (cy/ +) derived renal cells, but only a few from control rat renal cells. In contrast, when cultivated on plastic as monolayer cultures, Han:SPRD (cy/ +)-derived and control rat-derived renal cells were indistinguishable and did not form cyst-like structures. Immunohistochemical characterization of the cyst-like structures suggests tubular epithelial origin of the cyst-forming cells. The amount of cysts formed from Han:SPRD (cy/ +)-derived renal cells grown in a stationary suspension culture is susceptible to modulation by different conditions. Human cyst fluid and epidermal growth factor both stimulated the formation of cysts from Han:SPRD (cy/ +)-derived renal cells whereas taxol inhibited cystogenesis. In contrast, neither human cyst fluid nor epidermal growth factor affected the amount of cysts formed by control rat renal cells. As the culture model reported here allows not only the distinction of PKD-derived tubular epithelium from its normal counterpart, but also the modulation of cyst formation especially by Han:SPRD (cy/ +)-derived renal cells, it might be a useful prescreening protocol for potential treatments for PKD and thus reduce the need for animal experiments. Both authors contributed equally to the work.     

Towards a framework for the evolutionary genomics of Kinetoplastids: what kind of data and how much?

The current status of kinetoplastids phylogeny and evolution is discussed in view of the recent progresses on genomics. Some ideas on a potential framework for the evolutionary genomics of kinetoplastids are presented.