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Cell quiescence appeared early in evolution as an adaptive response to adverse conditions, i.e. nutrient depletion. In metazoans, quiescence has been enrolled in additional purposes like tissue homeostasis, which is made possible by the presence of adult stem cells (ASCs). Cell-cycle control machinery is a common hub for quiescence entrance, and evidence indicates a role for p53 in establishing the quiescent state of undamaged cells. Mechanisms responsible for waking up quiescent cells remain elusive and nutritional stimulus, as a legacy of its original role, still appears to be a player in quiescence exit. Planarians, rich in ASCs, represent a suitable system in which we characterized a quiescent population of ASCs, the dorsal midline cord (DMC) cells, exhibiting unique transcriptional features and maintained quiescent by p53 and awakened upon feeding. The function of DMC cells is puzzling and we speculate that DMC cells, despite retaining ancient properties, might represent a functional drift in which quiescence has been recruited to provide evolutionary advantages.

Background: Long acting injectable (LAI) antipsychotics have been claimed to ensure treatment adherence and possibly reduce the daily burden of oral formulations. So far, only surveys investigating the theoretical prescribing attitudes of clinicians have been employed. On this basis, we aimed to investigate reasons for prescribing LAIs in a real-world, unselected sample of patients. Methods: The STAR Network Depot Study is an observational, multicentre study consecutively enrolling adults initiating a LAI over a 12-months period. Clinical severity was assessed with the Brief Psychiatric Rating Scale, and patient’s attitude toward medications with the Drug Attitude Inventory 10 items. Psychiatrists recorded reasons for LAI prescribing for each study participant. Responses were grouped into six non-mutually exclusive categories: aggressiveness, patient engagement, ease of drug taking, side-effects, stigma, adherence. Results: Of the 451 patients included, two-thirds suffered from chronic psychoses. Improving patient engagement with the outpatient psychiatric service was the most common reason for prescribing LAIs (almost 80% of participants), followed by increasing treatment adherence (57%), decreasing aggressiveness (54%), and improving ease of drug taking (52%). After adjusting for confounders, logistic regression analyses showed that reasons for LAI use were associated with LAI choice (e.g. first-generation LAIs for reducing aggressiveness). Conclusion: Despite the wide availability of novel LAI formulation and the emphasis on their wider use, our data suggest that the main reasons for LAI use have remained substantially unchanged over the years, focusing mostly on improving patient’s engagement. Further, clinicians follow implicit prescribing patterns when choosing LAIs, and this may generate hypotheses for future experimental studies.

Inflammation-driven tissue remodelling may develop to fibrotic rearrangement. With regard to inflammatory bowel diseases, fibrotic remodelling has been evaluated in Crohn’s disease, while little attention to such processes has been paid to ulcerative colitis (UC) [1]. The present study evaluated the distribution of connective tissue and angiogenesis in colon of patients with UC, paying particular attention to the tonaca muscularis, which is poorly considered in histopathological studies. Full-thickness left colonic samples were obtained from 10 patients with established, severe and pharmacologically unresponsive UC, who underwent bowel resection. Routine histology, histochemistry and immunohistochemistry were conducted in paraffin cross-sections. The distribution of collagen and elastic fibers was evaluated and quantified by both histochemical (Van Gieson, orcein, Verroheff staining) and immunohistochemical (anti-collagen I and III, anti-elastin) assays. The vascular network pattern was studied by anti-CD31 and nestin immunostaining. For comparison, the same evaluations were performed in healthy colonic control samples obtained from 10 subjects, who underwent surgery for uncomplicated colon cancer. A significant increase in collagen fibers and a decrease in elastin content were detected in the UC inflamed colon, as compared with controls. In particular, enhanced collagen deposition (mainly collagen type III) were found at level of submucosa, and tonaca muscularis within the longitudinal muscle (mainly along the serosal side) and circular muscle layer, and in perivascular connective tissue. By contrast, elastic fibers were significantly reduced throughout the whole muscle compartment, with particular regard for the myenteric ridge. Microvessel density was significantly higher in both submucosa and tonaca muscularis of colonic samples from UC patients compared with those from healthy control individuals. The present findings indicate that a significant tissue remodelling occurs in the inflamed colonic wall in patients with UC, also at the level of muscle layers. This rearrangement of the connective fibers and vascular network, together with the known alterations affecting the myenteric neurons and interstitial cells of Cajal, may contribute to the development of enteric dysmotility, and, accordingly, to the serious digestive symptoms which afflict patients with UC., Italian Journal of Anatomy and Embryology, Vol 117, No 2 (Supplement) 2012

Objective Gut fibrosis occurs under chronic inflammation. This study examined the effects of different cyclooxygenase (COX) inhibitors on fibrosis in the inflamed colon. Methods Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS) in albino male Sprague–Dawley rats. After 6, 12 and 18 days, macroscopic and microscopic damage, collagen and elastic fibre content were examined. At day 6, pro-fibrotic factors (collagen I and III, hydroxyproline, fibronectin, matrix metalloproteinase-2 and -9), transforming growth factor-beta (TGF-β) signalling [TGF-β, Ras homolog gene family member A (RhoA), phosphorylated small mother against decapentaplegic (pSMAD)-2 and -6] and peristalsis were assessed, and the effects of indomethacin, SC-560 or celecoxib were tested. Key findings Six days after DNBS administration, significant histopathological signs of fibrotic remodelling were observed in rats. At day 6, pro-fibrotic factors were up-regulated and colonic peristalsis was altered. COX inhibitors reversed the histochemical, molecular and functional changes in the fibrotic colon. COX inhibition reduced TGF-β expression, SMAD2 phosphorylation and RhoA, and increased SMAD6 expression. Conclusions Colonic fibrosis is associated with altered bowel motility and induction of profibrotic factors driven by TGF-β signalling. COX-1 and COX-2 inhibition counteracts this fibrotic remodelling by the modulation of TGF-β/SMAD signalling, mainly via SMAD6 induction and reduction in SMAD2 phosphorylation.

Tau displacement from microtubules is the first step in the onset of tauopathies and is followed by toxic protein aggregation. However, other non-canonical functions of Tau might have a role in these pathologies. Here, we demonstrate that a small amount of Tau localizes in the nuclear compartment and accumulates in both the soluble and chromatin-bound fractions. We show that favoring Tau nuclear translocation and accumulation, by Tau overexpression or detachment from MTs, increases the expression of VGluT1, a disease-relevant gene directly involved in glutamatergic synaptic transmission. Remarkably, the P301L mutation, related to frontotemporal dementia FTDP-17, impairs this mechanism leading to a loss of function. Altogether, our results provide the demonstration of a direct physiological role of Tau on gene expression. Alterations of this mechanism may be at the basis of the onset of neurodegeneration.