Publications by authors named "Kay T"

Background: The harmonious operation of many insect societies depends upon colony-wide dissemination of a non-volatile pheromone produced by a single queen, which informs workers of her presence. This represents a major challenge in large colonies. Honeybee colonies, which can exceed 60,000 bees, are believed to solve this challenge using 'messenger' workers that actively relay the queen pheromone throughout the hive.

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Type 1 diabetes (T1D) is an autoimmune disease that develops when T cells destroy the insulin-producing beta cells that reside in the pancreatic islets. Immune cells, including T cells, infiltrate the islets and gradually destroy the beta cells. Human islet-infiltrating CD4 T cells recognize peptide epitopes derived from proinsulin, particularly C-peptide.

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Transcription through chromatin under torsion represents a fundamental problem in biology. Pol II must overcome nucleosome obstacles and, because of the DNA helical structure, must also rotate relative to the DNA, generating torsional stress. However, there is a limited understanding of how Pol II transcribes through nucleosomes while supercoiling DNA.

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Article Synopsis
  • DNA replication and transcription happen at the same time on the same DNA, which can create conflicts between the replisome and RNA polymerase, potentially causing genome instability.
  • Research shows that collisions between RNA polymerase and the replication fork are more harmful when they come from opposite directions (head-on) compared to when they run in the same direction (co-directional), but the exact reasons behind this aren't fully understood.
  • The study found that RNA polymerase binds more stably in head-on conflicts, especially with longer RNA transcripts, which enhances its ability to block replication; an RNA-DNA hybrid forms during this process, creating additional complications for the replication fork but could also help initiate replication on the lagging strand.
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  • * Current research seeks to understand T1D and develop new treatments, including immune system modulation, β-cell regeneration, and advanced insulin delivery methods like closed-loop pumps and stem cell therapies.
  • * Recent studies suggest that TNF-α inhibitors could help preserve β-cell function in people with advanced T1D, prompting experts to convene and plan pivotal clinical trials to further evaluate their effectiveness.
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  • Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is linked to a CAG repeat expansion in the ATXN3 gene, with longer repeats leading to earlier disease onset and increased intergenerational anticipation.
  • Researchers used advanced sequencing techniques to analyze the ATXN3 repeat and somatic expansion in individuals from the Azores, finding issues with traditional measurement methods that could affect understanding of clinical outcomes.
  • The study indicated that while age and CAG repeat length influence somatic expansion, the age factor was more significant, and a specific single nucleotide variant was associated with the expansion rate, highlighting the potential for using ATXN3 repeat analysis in clinical trials.
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The ecological success of social insects makes their colony organization fascinating to scientists studying collective systems. In recent years, the combination of automated behavioural tracking and social network analysis has deepened our understanding of many aspects of colony organization. However, because studies have typically worked with single species, we know little about interspecific variation in network structure.

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Unlabelled: Gut microbes can impact cognition and behavior, but whether they regulate the division of labor in animal societies is unknown. We addressed this question using honeybees since they exhibit division of labor between nurses and foragers and because their gut microbiota can be manipulated. Using automated behavioral tracking and controlling for co-housing effects, we show that gut microbes influence the age at which bees start expressing foraging-like behaviors in the laboratory but have no effects on the time spent in a foraging arena and number of foraging trips.

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Chronic destruction of insulin-producing pancreatic β cells by T cells results in autoimmune diabetes. Similar to other chronic T cell-mediated pathologies, a role for T cell exhaustion has been identified in diabetes in humans and NOD mice. The development and differentiation of exhausted T cells depends on exposure to Ag.

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Social support refers to the help someone receives emotionally or instrumentally from their social network. Poor social support in the perinatal period has been associated with increased risk for symptoms of common mental disorders, including depression and posttraumatic stress symptoms (PTS), which may impact parenting behavior. Whether social support impacts parenting behaviors, independent of mental health symptomatology, remains unclear.

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Introduction: Chronic activation of self-reactive T cells with beta cell antigens results in the upregulation of immune checkpoint molecules that keep self-reactive T cells under control and delay beta cell destruction in autoimmune diabetes. Inhibiting PD1/PD-L1 signaling results in autoimmune diabetes in mice and humans with pre-existing autoimmunity against beta cells. However, it is not known if other immune checkpoint molecules, such as TIGIT, can also negatively regulate self-reactive T cells.

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Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD) is a heritable proteinopathy disorder, whose causative gene, ATXN3, undergoes alternative splicing. Ataxin-3 protein isoforms differ in their toxicity, suggesting that certain ATXN3 splice variants may be crucial in driving the selective toxicity in SCA3. Using RNA-seq datasets we identified and determined the abundance of annotated ATXN3 transcripts in blood (n = 60) and cerebellum (n = 12) of SCA3 subjects and controls.

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Article Synopsis
  • - Persistent exposure to antigens leads to the development of exhausted T cells, which are less effective in responding to threats, and this phenomenon typically occurs during chronic infections and cancer, raising questions about its role in autoimmune diabetes.
  • - In a study using nonobese diabetic (NOD) mice, exhausted CD8+ T cells targeting the islet antigen IGRP were found in the pancreas, while more of these cells were preserved in peripheral lymphoid organs.
  • - By creating transgenic NOD mice that express IGRP in cells outside the islet, researchers showed that exposure to IGRP in these extraislet areas resulted in severely exhausted T cells, which ultimately protected the mice from developing diabetes.
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β-cells are a type of endocrine cell found in pancreatic islets that synthesize, store and release insulin. In type 1 diabetes (T1D), T-cells of the immune system selectively destroy the insulin-producing β-cells. Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival.

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Objective: This multicenter prospective cohort study compared pancreas volume as assessed by MRI, metabolic scores derived from oral glucose tolerance testing (OGTT), and a combination of pancreas volume and metabolic scores for predicting progression to stage 3 type 1 diabetes (T1D) in individuals with multiple diabetes-related autoantibodies.

Research Design And Methods: Pancreas MRI was performed in 65 multiple autoantibody-positive participants enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention study. Prediction of progression to stage 3 T1D was assessed using pancreas volume index (PVI), OGTT-derived Index60 score and Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), and a combination of PVI and DPTRS.

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Background: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction.

Methods: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma.

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Introduction: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria.

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Ants can particularly make for harmful pests, infesting human homes and reducing crop yields. The damage caused by ants and the efforts to mitigate the damage are hugely costly. Broad-spectrum insecticides are used most commonly; however, due to their negative side effects, there is increasing interest in nontoxic alternatives.

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Article Synopsis
  • A phase 2 trial investigated the effects of baricitinib, a JAK inhibitor, on β-cell function in patients with early-stage type 1 diabetes, comparing it to a placebo over 48 weeks.
  • Results showed that the baricitinib group had a significantly higher mean C-peptide level, indicating better β-cell function, and required a lower daily insulin dose compared to the placebo group.
  • While baricitinib improved certain measures of insulin production and glycemic control, the overall levels of glycated hemoglobin were similar between both groups, with no notable differences in adverse events reported.
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Coeliac artery (CA) injuries are an extremely rare subset of blunt abdominal trauma with a reported incidence of only 0.01%. Patterns of CA injury include intimal tear, dissection, thrombosis and pseudoaneurysm, with the most rare being complete CA avulsion.

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Objective: To evaluate the screening test accuracy and reliability of the parent-report preschool Strengths and Difficulties Questionnaire (P-SDQ) in primary care settings.

Methods: Children 24 to 48 months were recruited at scheduled primary care visits in Toronto, Canada. Parents completed the P-SDQ at baseline, 2, and 12 weeks.

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Aims: There is a need for interventions that meet the needs of low socioeconomic status (SES) groups, to encourage the adoption of healthy diets and physical activity, in line with current public health guidance. This qualitative research used co-production, a method which actively involves the relevant community, to identify and describe public health interventions to support a group of mothers of young children living in a low SES area.

Methods: A group of 20 mothers took part in three in-depth qualitative interviews to discuss in detail the type of support that would be of value to them for the adoption and maintenance of healthy behaviours.

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Social isolation negatively affects health, induces detrimental behaviors, and shortens lifespan in social species. Little is known about the mechanisms underpinning these effects because model species are typically short-lived and non-social. Using colonies of the carpenter ant Camponotus fellah, we show that social isolation induces hyperactivity, alters space-use, and reduces lifespan via changes in the expression of genes with key roles in oxidation-reduction and an associated accumulation of reactive oxygen species.

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CXCL10 is an IFNγ-inducible chemokine implicated in the pathogenesis of type 1 diabetes. T-cells attracted to pancreatic islets produce IFNγ, but it is unclear what attracts the first IFNγ -producing T-cells in islets. Gut dysbiosis following administration of pathobionts induced CXCL10 expression in pancreatic islets of healthy non-diabetes-prone (C57BL/6) mice and depended on TLR4-signaling, and in non-obese diabetic (NOD) mice, gut dysbiosis induced also CXCR3 chemokine receptor in IGRP-reactive islet-specific T-cells in pancreatic lymph node.

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