ALDH1 as a functional marker of cancer stem and progenitor cells

Stem cells have now been described in a variety of tissues, even in those where the cells' turn over rate is slow, such as the brain and the resting mammary gland. There is also accumulating evidence that tumors are derived from and are maintained by a rare population of dysregulated stem cells. However, discrepancies in the markers used and reported have slowed down the functional characterization of these somatic stem cells. To circumvent this challenging issue, universal stem cell markers with properties common to all stem cell types must be discovered and exploited. In line with this idea, the measurement of aldehyde dehydrogenase isoform 1 (ALDH1) activity shows promising potential as a universal marker for the identification and isolation of stem cells from multiple sources. Herein, we review the available data reporting utilization of ALDH1 activity as a means to identify and isolate stem cells and cancer stem cells, with a special focus on the mammary gland and breast cancer.     

Selective human endothelial cell activation by chemokines as a guide to cell homing

An original model of organo-specific, immortalized and stabilized endothelial cell lines was used to delineate the part played by some chemokines (CCL21, CX3CL1, CCL5 and CXCL12) and their receptors in endothelium organo-specificity. Chemokine receptor expression and chemokine presentation were investigated on organo-specific human endothelial cell lines. Although the chemokines showed distinct binding patterns for the various endothelial cell lines, these were not correlated with the expression of the corresponding receptors (CX3CR1, CXCR4, CCR5 and CCR7). Experiments with CCL21 on peripheral lymph node endothelial cells demonstrated that the chemokine did not co-localize with its receptor but was associated with extracellular matrix components. The specific activity of chemokines was clearly shown to be related to the endothelial cell origin. Indeed, CX3CL1 and CCL21 promoted lymphocyte recruitment by endothelial cells from the appendix and peripheral lymph nodes, respectively, while CX3CL1 pro-angiogenic activity was restricted to endothelial cells from the appendix and skin. The high specificity of the chemokine/endothelium interaction allowed the design of a direct in vitro endothelial cell targeting assay. This unique cellular model demonstrated a fundamental role for chemokines in conferring on the endothelium its organo-specificity and its potential for tissue targeting through the selective binding, presentation and activation properties of chemokines.     

Expression of c-Fos and CRF in the brains of rats differing in the strength of a fear response

The aim of the study was to examine the neurochemical background of differences in the individual responses to conditioned aversive stimuli, using the strength of a rat conditioned freezing response (the contextual fear test), as a discriminating variable. It was shown that low responders (LR), i.e. rats with duration of a freezing response one standard error, or more, below the mean value, had a higher activity of the M2 cortical area, and the median raphe nucleus (c-Fox expression), in comparison to the high responders (HR), i.e. rats with the duration of a freezing response one standard error, or more, above the mean value. These animals had also stronger 5-HT- and CRF-related immunostaining in the M2 area, and increased concentration of GABA in the basolateral nucleus of amygdala (in vivo microdialysis). The LR group vocalized more during test session in the aversive band, and had higher serum levels of corticosterone, examined 10 min after test session. It was shown that different natural patterns of responding to conditioned aversive stimuli are associated with different involvement of brain structures and with dissimilar neurochemical mechanisms.     

Diabetic cardiomyopathy: a controversial entity: reply

We are most grateful to Dr Karamitsos et al. for showing suchan avid interest in our paper.¹ Upon its submission, we wereacutely aware that we might well shake things up, as prior toconfronting the actual study results we also used to supportthe notion of diabetic     

Stricture dilation after laparoscopic Roux-en-Y gastric bypass

BACKGROUND: In surgical treatment of morbid obesity, maintaining a restrictive anastomosis is key to long-range success. However, laparoscopic Roux-en-Y gastric bypass (LRYGB) may result in gastrojejunal (GJ) stricture, requiring treatment in up to 27% of patients. METHODS: This is a retrospective review of the outcome of 223 consecutive LRYGB patients. Patients developing stricture received standard endoscopic balloon dilation by the same surgeon. Stricture and nonstricture groups were compared for excess body weight loss (EBWL) at 1, 3, 6, and 12 months. RESULTS: GJ stricture requiring dilation occurred in 38 patients (17%). After dilation all patients were relieved of stricture symptoms and none required revision. By 12 months, patients with stricture had an EBWL of 86% compared with nonstrictured patients at 75%. CONCLUSION: Endoscopic balloon dilation is a safe and effective treatment option for GJ stricture. Improved weight loss occurred for patients with stricture requiring dilation.     

S1P1 deletion in oligodendroglial lineage cells: Effect on differentiation and myelination

Sphingosine 1‐phosphate (S1P) receptors are G protein‐coupled receptors expressed by many cell types, including cells of oligodendrocyte (OLG) lineage. We had previously shown that targeted deletion of S1P₁ in OLG lineage cells did not result in obvious clinical phenotype or altered number of OLGs at 3 months, but there were subtle abnormalities in myelin. In this study, we examined the role of S1P₁ in developmental myelination and cell survival, focusing on age 3 weeks. We found that S1P₁ deficiency led to delayed differentiation of OLG progenitors (OPCs) into OLGs that is independent of p38 phosphorylation. This was accompanied by decreased levels of myelin basic protein (MBP) but not of myelin‐OLG glycoprotein (MOG), and slight decrease in myelin thickness in the corpus callosum of S1P₁ conditional knockout (CKO) mice. S1P₁‐deficient OLGs exhibited slower process extension, which was associated with attenuated phosphorylation of extracellular signal regulated kinases (ERKs) and p21‐activated kinases (PAKs), and with upregulation of tropomodulin1. Basal levels of pAkt were not affected, though expectedly, no response to a selective S1P₁ agonist SEW2871 was observed. S1P₁‐deficient OLGs did not exhibit increased cell death in response to cuprizone, tumor necrosis factor‐α, or deprivation of nutrients and growth factors. We conclude that S1P₁ signaling regulates OLG development, morphological maturation and early myelination. GLIA 2016;64:570–582