Effects of ancient and modern, avoidant and approach stimuli on visual search task reaction times

The threat superiority effect refers to faster and more accurate detection of fearful stimuli. This has been explained as evidence for evolution, as ancient fearful stimuli are detected more quickly than modern fearful stimuli. The aim of this study was to investigate which of two alternate evolutionary explanations best explains the findings. Whereas Ohman and Mineka (2001) dealt only with avoidant responses, Lang suggested that stimuli may evoke either an avoidant (fearful) or approach response, associated with negative or positive valence, respectively. The experiment employed a same-different task where Age (ancient, modern), and Valence (approach, avoidant, neutral) were manipulated and presented to 37 (19 females and 18 males) participants. Participants were presented with slides of 9 images, and asked to determine whether all images come from the same category (for example they are all flowers) or a different category (there is a snake among the flowers) as quickly and as accurately as possible. Ancient approach (horses) and avoidant (snakes) stimuli were detected faster than the neutral stimuli (mushrooms), but both modern approach (pizzas) and modern neutral (clocks) stimuli were detected faster than avoidant (guns) stimuli. These findings are most consistent with the evolutionary explanation of Lang (1995). It is suggested that the disparate results in the literature may be due to confounds associated with stimulus similarity

Mindfulness-based treatment for bipolar disorder: A systematic review of the literature

Despite the increasing number of studies examining the effects of mindfulness interventions on symptoms associated with Bipolar Disorder (BD), the effectiveness of this type of interventions remains unclear. The aim of the present systematic review was to (i) critically review all available evidence on Mindfulness Based Cognitive Therapy (MBCT) as a form of intervention for BD; (ii) discuss clinical implications of MBCT in treating patients with BD; and (iii) provide a direction for future research. The review presents findings from 13 studies (N = 429) that fulfilled the following selection criteria: (i) included BD patients; (ii) presented results separately for BD patients and control groups (where a control group was available); (iii) implemented MBCT intervention; (iv) were published in English; (v) were published in a peer reviewed journal; and (vi) reported results for adult participants. Although derived from a relatively small number of studies, results from the present review suggest that MBCT is a promising treatment in BD in conjunction with pharmacotherapy. MBCT in BD is associated with improvements in cognitive functioning and emotional regulation, reduction in symptoms of anxiety depression and mania symptoms (when participants had residual manic symptoms prior to MBCT). These, treatment gains were maintained at 12 month follow up when mindfulness was practiced for at least 3 days per week or booster sessions were included. Additionally, the present review outlined some limitations of the current literature on MBCT interventions in BD, including small study sample sizes, lack of active control groups and idiosyncratic modifications to the MBCT intervention across studies. Suggestions for future research included focusing on factors underlying treatment adherence and understanding possible adverse effects of MBCT, which could be of crucial clinical importance

Optimisation of protocols for ex vivo expansion of limbal stem cells and their enrichment

Ph. D. ThesisThe corneal epithelial cells are constantly replaced by the stem cells located at the limbus, the peripheral edge of the cornea, therefore known as limbal stem cells (LSCs). LSCs can be destroyed by numerous factors which results in the condition called limbal stem cell deficiency (LSCD). Ex vivo expansion of LSCs is a well-established technique used successfully to cure patients with LSCD. Therapeutic use of LSCs must be performed in compliance with good manufacturing practice (GMP) as a quality assurance system. However, traditional culture media for ex vivo expansion of LSCs contains a number of ingredients derived from animal sources which may compromise its safety profile for human transplantation. The first aim of the study was to define new GMP grade medium for cultivation and maintenance of LSCs in vitro. Formulation of new GMP compliant media resulted in equal growth to non-GMP grade media. Strick regulations for cell therapy promote centralization of culture units, therefore definition of reliable and practical transportation strategies is vitally important. The second aim of this study was to optimise the transport conditions for limbal biopsies (LBs) and cultured limbal epithelial cells (LECs). Transport of LBs at room temperature proved to be significantly superior to 4°C transport. We also showed that cultured LECs may be stored in serumfree media and transported up to 7 days at 23°C without any negative effect on cell number, viability, colony forming efficiency or gene expression profile. Due to the absence of specific LSC markers, identification and isolation of putative LSCs is a complicated task. The third and final aim of this study was to identify novel cell surface markers for LSCs. We reported herein the identification of a new cell surface marker for LSCs (CD200) as well as a cell surface marker for proliferating progenitor cells (CD109)

The role of autophagy in immunity and autoimmune diseases

© 2014 University of Kragujevac, Faculty of Science. All rights reserved. Autophagy is a catabolic mechanism in the cell that involves the degradation of unnecessary or dysfunctional cellular components by the lysosomal machinery. Recent studies have indicated that autophagy is a source of autoantigens, thus highlighting its potential role in the pathogenesis of autoimmunity. Th ere are at least three diff erent forms of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA). Th e physiological role of autophagy is to maintain cellular homeostasis by removing long-lived, damaged proteins and dysfunctional organelles and by providing energy. Aberrant autophagy may contribute to chronic infl ammatory diseases and autoimmune diseases. An understanding of the complex relationships between autophagy and autophagy-related genes in each autoimmune disease creates the possibility of developing more specifi c and eff ective therapeutic strategies. Given the importance of autophagy in immune functions, this review article summarises current knowledge about the role of autophagy in the pathogenesis of autoimmune diseases

Seeding hESCs to achieve optimal colony clonality

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have promising clinical applications which often rely on clonally-homogeneous cell populations. To achieve this, cross-contamination and merger of colonies should be avoided. This motivates us to experimentally study and quantitatively model the growth of hESC colonies. The colony population is unexpectedly found to be multi-modal. We associate these sub-populations with different numbers of founding cells, and predict their occurrence by considering the role of cell-cell interactions and cell behaviour on randomly seeded cells. We develop a multi-population stochastic exponential model for the colony population which captures our experimental observations, and apply this to calculate the timescales for colony merges and over which colony size no longer predicts the number of founding cells. These results can be used to achieve the best outcome for homogeneous colony growth from different cell seeding densities

Therapeutic efficacy of mesenchymal stem cells for cardiovascular diseases

Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy of CVDs. In particular, we analyze the biological properties of MSCs, elucidate recent clinical findings and clinical trial phases of investigation, highlight clinical therapeutic effects of MSCs, and discuss challenges towards the clinical use of these cells in the therapy of CVDs

Winter is coming: the future of cryopreservation.

The preservative effects of low temperature on biological materials have been long recognised, and cryopreservation is now widely used in biomedicine, including in organ transplantation, regenerative medicine and drug discovery. The lack of organs for transplantation constitutes a major medical challenge, stemming largely from the inability to preserve donated organs until a suitable recipient is found. Here, we review the latest cryopreservation methods and applications. We describe the main challenges-scaling up to large volumes and complex tissues, preventing ice formation and mitigating cryoprotectant toxicity-discuss advantages and disadvantages of current methods and outline prospects for the future of the field

An iPSC Patient Specific Model of CFH (Y402H) Polymorphism Displays Characteristic Features of AMD and Indicates a Beneficial Role for UV Light Exposure

Age related macular degeneration (AMD) is the most common cause of blindness, accounting for 8.7% of all blindness globally. Vision loss is caused ultimately by apoptosis of the retinal pigment epithelium (RPE) and overlying photoreceptors. Treatments are evolving for the wet form of the disease, however these do not exist for the dry form. Complement factor H (CFH) polymorphism in exon 9 (Y402H) has shown a strong association with susceptibility to AMD resulting in complement activation, recruitment of phagocytes, retinal pigment epithelium (RPE) damage and visual decline. We have derived and characterised induced pluripotent stem cell (iPSCs) lines from two patients without AMD and low risk genotype and two patients with advanced AMD and high risk genotype and generated RPE cells that show local secretion of several proteins involved in the complement pathway including factor H (FH), factor I (FI) and factor H like 1 (FHL-1). The iPSC RPE cells derived from high risk patients mimic several key features of AMD including increased inflammation and cellular stress, accumulation of lipid droplets, impaired autophagy and deposition of “drüsen” like deposits. The low and high risk RPE cells respond differently to intermittent exposure to UV light which leads to an improvement in cellular and functional phenotype only in the high risk AMD-RPE cells. Taken together our data indicate that the patient specific iPSC model provides a robust platform for understanding the role of complement activation in AMD, evaluating new therapies based on complement modulation and drug testing

Gal-3 plays an important pro-inflammatory role in the induction phase of acute colitis by promoting activation of NLRP3 inflammasome and production of IL-β in macrophages

BACKGROUND AND AIMS: Galectin-3 [Gal-3] is an endogenous lectin with a broad spectrum of immunoregulatory effects: it plays an important role in autoimmune/inflammatory and malignant diseases, but the precise role of Gal-3 in pathogenesis of ulcerative colitis is still unknown. METHODS: We used a model of dextran sulphate sodium [DSS]-induced acute colitis. The role of Gal-3 in pathogenesis of this disease was tested by evaluating disease development in Gal-3 deficient mice and administration of Gal-3 inhibitor. Disease was monitored by clinical, histological, histochemical, and immunophenotypic investigations. Adoptive transfer was used to detect cellular events in pathogenesis. RESULTS: Genetic deletion or pharmacological inhibition of Gal-3 significantly attenuate DSS-induced colitis. Gal-3 deletion suppresses production of pro-inflammatory cytokines in colonic macrophages and favours their alternative activation, as well as significantly reducing activation of NOD-like receptor family, pyrin domain containing 3 [NLRP3] inflammasome in macrophages. Peritoneal macrophages isolated from untreated Gal-3(-/-) mice and treated in vitro with bacterial lipopolysaccharide or DSS produce lower amounts of tumour necrosis factor alpha [TNF-α] and interleukin beta [IL-1β] when compared with wild type [WT] cells. Genetic deletion of Gal-3 did not directly affect total neutrophils, inflammatory dendritic cells [DCs] or natural killer [NK] T cells. However, the total number of CD11c+ CD80+ DCs which produce pro-inflammatory cytokines, as well as TNF-α and IL-1β producing CD45+ CD11c- Ly6G+ neutrophils were significantly lower in colons of Gal-3(-/-) DSS-treated mice. Adoptive transfer of WT macrophages significantly enhanced the severity of disease in Gal-3(-/-) mice. CONCLUSIONS: Gal-3 expression promotes acute DSS-induced colitis and plays an important pro-inflammatory role in the induction phase of colitis by promoting the activation of NLRP3 inflammasome and production of IL-1β in macrophages

Human induced pluripotent stem cells generate light responsive retinal organoids with variable and nutrient dependent efficiency

The availability of in vitro models of the human retina in which to perform pharmacological and toxicological studies is an urgent and unmet need. An essential step for developing in vitro models of human retina is the ability to generate laminated, physiologically functional and light-responsive retinal organoids from renewable and patient specific sources. We investigated five different human induced pluripotent stem cell (iPSC) lines and showed a significant variability in their efficiency to generate retinal organoids. Despite this variability, by month 5 of differentiation, all iPSC-derived retinal organoids were able to generate light responses, albeit immature, comparable to the earliest light responses recorded from the neonatal mouse retina, close to the period of eye opening. All iPSC-derived retinal organoids exhibited at this time a well-formed outer nuclear like layer containing photoreceptors with inner segments, connecting cilium and outer like segments. The differentiation process was highly dependent on seeding cell density and nutrient availability determined by factorial experimental design. We adopted the differentiation protocol to a multiwell plate format which enhanced generation of retinal organoids with retinal pigmented epithelium (RPE) and improved ganglion cell development and the response to physiological stimuli. We tested the response of iPSC-derived retinal organoids to Moxifloxacin and showed that similarly to in vivo adult mouse retina, the primary affected cell types were photoreceptors. Together our data indicate that light responsive retinal organoids derived from carefully selected and differentiation efficient iPSC lines can be generated at the scale needed for pharmacology and drug screening purposes. © AlphaMed Press 2018