Single-cell analysis of the T-cell receptor repertoire in untreated myeloma patients suggests potential myeloma-reactive CD8+ T-cells are shared between blood and marrow.

Not available.

The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in -Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines.

We have previously identified a parasite-derived peptide, FhHDM-1, that prevented the progression of diabetes in nonobese diabetic (NOD) mice. Disease prevention was mediated by the activation of the PI3K/Akt pathway to promote -cell survival and metabolism without inducing proliferation. To determine the molecular mechanisms driving the antidiabetogenic effects of FhHDM-1, miRNA:mRNA interactions and predictions of the gene networks were characterised in -cells, which were exposed to the proinflammatory cytokines that mediate -cell destruction in Type 1 diabetes (T1D), in the presence and absence of FhHDM-1.

Who feels happier right now?: The impact of temporal distance on children's judgements of emotional intensity.

Do children consider temporal distance in their reasoning about the world? Using a novel method that relied minimally on verbal ability, we asked N = 106 3- to 6-year-olds to judge which of two characters felt more 'happy'/'sad' right now: one engaging in a pleasant/unpleasant activity tomorrow or another engaging in this same activity when they are a year older. That is, we examined whether children understood that the closer in time a future event, the more intense the currently felt emotion. Starting at age 4, children correctly judged which child was more 'happy'/'sad' right now.

The helminth-derived peptide, FhHDM-1, reverses the trained phenotype of NOD bone-marrow-derived macrophages and regulates proinflammatory responses.

We implicate a phenotype of trained immunity in bone-marrow-derived macrophages in the onset and progression of type 1 diabetes in nonobese diabetic mice. Treatment with FhHDM-1 reversed immune training, reducing histone methylation and glycolysis, and decreasing proinflammatory cytokine production to the same level as macrophages from nondiabetic immune-competent BALB/c mice.

Tomorrow versus a year from now: Do children represent the near and distant future differently?

Adults represent the near future more concretely and vividly than the distant future, with important implications for future-oriented behavior (e.g., planning, self-control).

How do parasitic worms prevent diabetes? An exploration of their influence on macrophage and β-cell crosstalk.

Diabetes is the fastest growing chronic disease globally, with prevalence increasing at a faster rate than heart disease and cancer. While the disease presents clinically as chronic hyperglycaemia, two distinct subtypes have been recognised. Type 1 diabetes (T1D) is characterised as an autoimmune disease in which the insulin-producing pancreatic β-cells are destroyed, and type 2 diabetes (T2D) arises due to metabolic insufficiency, in which inadequate amounts of insulin are produced, and/or the actions of insulin are diminished.

The helminth derived peptide FhHDM-1 redirects macrophage metabolism towards glutaminolysis to regulate the pro-inflammatory response.

We have previously identified an immune modulating peptide, termed FhHDM-1, within the secretions of the liver fluke, , which is sufficiently potent to prevent the progression of type 1 diabetes and multiple sclerosis in murine models of disease. Here, we have determined that the FhHDM-1 peptide regulates inflammation by reprogramming macrophage metabolism. Specifically, FhHDM-1 switched macrophage metabolism to a dependence on oxidative phosphorylation fuelled by fatty acids and supported by the induction of glutaminolysis.

Pancreatic Transdifferentiation Using β-Cell Transcription Factors for Type 1 Diabetes Treatment.

Type 1 diabetes is a chronic illness in which the native beta (β)-cell population responsible for insulin release has been the subject of autoimmune destruction. This condition requires patients to frequently measure their blood glucose concentration and administer multiple daily exogenous insulin injections accordingly. Current treatments fail to effectively treat the disease without significant side effects, and this has led to the exploration of different approaches for its treatment.

Exploring the role of macrophages in determining the pathogenesis of liver fluke infection.

The food-borne trematodes, and , are classified as group 1 biological carcinogens: definitive causes of cancer. By contrast, infections with , also a food-borne trematode of the phylum Platyhelminthes, are not carcinogenic. This review explores the premise that the differential activation of macrophages during infection with these food-borne trematodes is a major determinant of the pathological outcome of infection.

Targeting the PI3K/Akt signaling pathway in pancreatic β-cells to enhance their survival and function: An emerging therapeutic strategy for type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of the insulin-producing β-cells within the pancreas. Islet transplantation represents one cure; however, during islet preparation and post transplantation significant amounts of β-cell death occur. Therefore, prevention and cure of T1D is dependent upon the preservation of β-cell function and the prevention of β-cell death.

Recall, response bias and recognition are differentially impacted by social anxiety irrespective of feedback modality.

Background And Objectives: This study replicates and extends Houle-Johnson et al.'s (2019) findings to better understand the role of feedback modality, ambiguity and social anxiety in the recognition and recall of self-relevant feedback.

Methods: Participants gave a speech and were provided with positive, negative, and ambiguous feedback via written text, (n = 33) or recorded sentences (n = 31) and later completed a recognition and recall task for the feedback.

The parasite-derived peptide FhHDM-1 activates the PI3K/Akt pathway to prevent cytokine-induced apoptosis of β-cells.

Type 1 diabetes (T1D) is an autoimmune disease characterised by the destruction of the insulin-producing beta (β)-cells within the pancreatic islets. We have previously identified a novel parasite-derived molecule, termed Fasciola hepatica helminth defence molecule 1 (FhHDM-1), that prevents T1D development in non-obese diabetic (NOD) mice. In this study, proteomic analyses of pancreas tissue from NOD mice suggested that FhHDM-1 activated the PI3K/Akt signalling pathway, which is associated with β-cell metabolism, survival and proliferation.

Neonatal Rats Exhibit a Predominantly Anti-Inflammatory Response following Spinal Cord Injury.

It has been reported that children may respond better than adults to a spinal cord injury (SCI) of similar severity. There are known biomechanical differences in the developing spinal cord that may contribute to this "infant lesion effect," but the underlying mechanisms are unknown. Using immunohistochemistry, we have previously demonstrated a different injury progression and immune cell response after a mild thoracic contusion SCI in infant rats, as compared to adult rats.

Tomorrow will be different: Children's ability to incorporate an intervening event when thinking about the future.

Future-oriented thought is ubiquitous in humans but challenging to study in children. Adults not only think about the future but can also represent a future state of the world that differs from the present. However, behavioral tasks to assess the development of future thought have not traditionally required children to do so as most can be solved based solely on representations of the present.

Use of a Hybrid Adeno-Associated Viral Vector Transposon System to Deliver the Insulin Gene to Diabetic NOD Mice.

Previously, we used a lentiviral vector to deliver furin-cleavable human insulin () to the livers in several animal models of diabetes using intervallic infusion in full flow occlusion (FFO), with resultant reversal of diabetes, restoration of glucose tolerance and pancreatic transdifferentiation (PT), due to the expression of beta (β)-cell transcription factors (β-TFs). The present study aimed to determine whether we could similarly reverse diabetes in the non-obese diabetic (NOD) mouse using an adeno-associated viral vector (AAV) to deliver - ± the β-TF to the livers of diabetic mice. The traditional AAV8, which provides episomal expression, and the hybrid AAV8/ that results in transgene integration were used.

Are all distances created equal? Insights from developmental psychology.

Gilead et al.'s theory presupposes that traversing temporal, spatial, social, and hypothetical distances are largely interchangeable acts of mental travel that co-occur in human ontogeny. Yet, this claim is at odds with recent developmental data suggesting that children's reasoning is differentially affected by the dimension which they must traverse, and that different representational abilities underlie travel across different dimensions.

The roles of perspective and language in children's ability to delay gratification.

Increasing psychological distance is an established method for improving children's performance in a number of self-regulation tasks. For example, using a delay of gratification (DoG) task, Prencipe and Zelazo (Psychological Science, 2005, Vol. 16, pp.

Expansion of Murine MSC Impairs Transcription Factor-Induced Differentiation into Pancreatic -Cells.

Combinatorial gene and cell therapy as a means of generating surrogate -cells has been investigated for the treatment of type 1 diabetes (T1D) for a number of years with varying success. One of the limitations of current cell therapies for T1D is the inability to generate sufficient quantities of functional transplantable insulin-producing cells. Due to their impressive immunomodulatory properties, in addition to their ease of expansion and genetic modification , mesenchymal stem cells (MSCs) are an attractive alternative source of adult stem cells for regenerative medicine.

Negative verbal self-relevant feedback is recognized with greater accuracy than facial feedback regardless of depression or social anxiety.

Background And Objectives: Self-referent information is critical for navigating the social realm, as we constantly use both verbal and non-verbal feedback in our interactions to understand ourselves and the world. In non-clinical samples, a memory bias for positive self-referent information has been observed, while a negativity bias has been observed among those with depression and anxiety. While research suggests that visual and auditory information is processed differently, no study has yet examined if memory biases persist for self-referent information presented by either means.

Partial pancreatic transdifferentiation of primary human hepatocytes in the livers of a humanised mouse model.

Background: Gene therapy is one treatment that may ultimately cure type 1 diabetes. We have previously shown that the introduction of furin-cleavable human insulin (INS-FUR) to the livers in several animal models of diabetes resulted in the reversal of diabetes and partial pancreatic transdifferentiation of liver cells. The present study investigated whether streptozotocin-diabetes could be reversed in FRG mice in which chimeric mouse-human livers can readily be established and, in addition, whether pancreatic transdifferentiation occurred in the engrafted human hepatocytes.

Targeting the master regulator mTOR: a new approach to prevent the neurological of consequences of parasitic infections?

A systematic analysis of 240 causes of death in 2013 revealed that parasitic diseases were responsible for more than one million deaths. The vast majority of these fatalities resulted from protozoan infections presenting with neurological sequelae. In the absence of a vaccine, development of effective therapies is essential to improving global public health.

Selection of reliable reference genes for the normalisation of gene expression levels following time course LPS stimulation of murine bone marrow derived macrophages.

Background: Macrophages are key players in the initiation, perpetuation and regulation of both innate and adaptive immune responses. They largely perform these roles through modulation of the expression of genes, especially those encoding cytokines. Murine bone marrow derived macrophages (BMDMs) are commonly used as a model macrophage population for the study of immune responses to pro-inflammatory stimuli, notably lipopolysaccharide (LPS), which may be pertinent to the human situation.

A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis.

Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines.

The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages.

The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1β, a cytokine that influences the development of both innate and adaptive immune responses. Helminth parasites secrete molecules that interact with innate immune cells, modulating their activity to ultimately determine the phenotype of differentiated T cells, thus creating an immune environment that is conducive to sustaining chronic infection. We show that one of these molecules, FhHDM-1, a cathelicidin-like peptide secreted by the helminth parasite, Fasciola hepatica, inhibits the activation of the NLRP3 inflammasome resulting in reduced secretion of IL-1β by macrophages.

Pancreatic Transdifferentiation and Glucose-Regulated Production of Human Insulin in the H4IIE Rat Liver Cell Line.

Due to the limitations of current treatment regimes, gene therapy is a promising strategy being explored to correct blood glucose concentrations in diabetic patients. In the current study, we used a retroviral vector to deliver either the human insulin gene alone, the rat NeuroD1 gene alone, or the human insulin gene and rat NeuroD1 genes together, to the rat liver cell line, H4IIE, to determine if storage of insulin and pancreatic transdifferentiation occurred. Stable clones were selected and expanded into cell lines: H4IIEins (insulin gene alone), H4IIE/ND (NeuroD1 gene alone), and H4IIEins/ND (insulin and NeuroD1 genes).