Recent Research Research Articles

Abstract 2299: More information from limited DNA: simultaneous measurement of genetics, 5hmC and 5mC in cell-free DNA

Abstract Liquid biopsy for profiling of cell free DNA (cfDNA) in blood holds huge promise to transform how we experience and manage cancer by early detection and identification of residual disease and subtype. While early work in liquid biopsy focused on the identification of actionable somatic variations at specific loci, the past decade has seen an expansion into non-genetic features, notably methylation. 5-methylcytosine (5-mC) profiles of cancer are differential from non-cancer at many more loci and so provide a stronger signal. Moreover, recent research has suggested that 5-hydroxymethylcytosine (5-hmC) profiles in cfDNA can be a marker for early cancer. However, a standard blood draw yields an average of only 10ng of cfDNA, presenting the dilemma of how to use limited sample to obtain maximum information. Existing methods for measuring methylation using next-generation sequencing cannot distinguish between 5-mC and 5-hmC and are limited in their ability to detect mutations, with approaches that measure both 5-mC and 5-hmC requiring two separate workflows. Hence, to measure complete genetics, 5-mC and 5-hmC using existing technologies requires three separate workflows, each of which require separate DNA input. We will present a technology which sequences at single base resolution the complete genetic sequence of input DNA fragments integrated with the modification status (unmodified, 5-mC or 5-hmC) for each CpG from low nanogram input quantities of DNA. A hairpin construct is used to create a copy of the original DNA strand. Enzymatic conversion followed by next-generation sequencing enables coupled decoding of bases across the original and copy strand, uniquely reporting one of A, C, G, T, 5-mC, or 5-hmC for each position in the input DNA fragment. Using this technology, we generated whole genome 6-letter data (measuring A, C, G, T, 5-mC, and 5-hmC at single-base resolution across the genome) on cell-free DNA extracted from plasma of healthy volunteers and patients with colorectal cancer at various stages of progression. We demonstrate how the technology can be used to compare 5-mC and 5-hmC methylomic profiles, genomics, and fragmentomics, across different stages of colorectal cancer. In particular, we show how disease progression can be marked by changes in 5-mC and 5-hmC across several loci. We propose that the ability to measure 5-mC and 5-hmC at high accuracy and single base resolution, alongside genomic and fragmentomic profiles, from a limited quantity of DNA will enable greater insight into the ctDNA in plasma and help advance the field of liquid biopsy towards fulfilling its promise. Citation Format: Tom J. Charlesworth, Fabio Puddu, Robert Crawford, Annelie Johansson, Ermira Lleshi, Aurelie Modat, Jamie Scotcher, Michael Wilson, Nicholas Harding, Jean Teyssandier, Jens Fullgrabe, Walraj Gosal, Paidi Creed. More information from limited DNA: simultaneous measurement of genetics, 5hmC and 5mC in cell-free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2299.

Sensitivity of Phonation Onset Pressure to Vocal Fold Stiffness Distribution.

Phonation onset is characterized by the unstable growth of vocal fold (VF) vibrations that ultimately results in self-sustained oscillation and the production of modal voice. Motivated by histological studies, much research has focused on the role of the layered structure of the vocal folds in influencing phonation onset, wherein the outer "cover" layer is relatively soft and the inner "body" layer is relatively stiff. Recent research, however, suggests that the body-cover (BC) structure over-simplifies actual stiffness distributions by neglecting important spatial variations, such as inferior-superior (IS) and anterior-posterior gradients and smooth transitions in stiffness from one histological layer to another. Herein, we explore sensitivity of phonation onset to stiffness gradients and smoothness. By assuming no a priori stiffness distribution and considering a second-order Taylor series sensitivity analysis of phonation onset pressure with respect to stiffness, we find two general smooth stiffness distributions most strongly influence onset pressure: a smooth stiffness containing aspects of BC differences and IS gradients in the cover, which plays a role in minimizing onset pressure, and uniform increases in stiffness, which raise onset pressure and frequency. While the smooth stiffness change contains aspects qualitatively similar to layered BC distributions used in computational studies, smooth transitions in stiffness result in higher sensitivity of onset pressure than discrete layering. These two general stiffness distributions also provide a simple, low-dimensional, interpretation of how complex variations in VF stiffness affect onset pressure, enabling refined exploration of the effects of stiffness distributions on phonation onset.

Engineering the activity and thermostability of a carboxylic acid reductase in the conversion of vanillic acid to vanillin

Vanillin is a valuable natural product that can be used as a fragrance and additive. Recent research in the biosynthesis of vanillin has brought attention to a key enzyme, carboxylic acid reductase (CAR), which catalyzes the reduction of vanillic acid to vanillin. Nevertheless, the biosynthesis of vanillin is hampered by the low activity and stability of CAR. As such, a rational design campaign was conducted on a well-documented carboxylic acid reductase from Segniliparus rugosus (SrCAR), using vanillic acid as the model substrate. After combined active site saturation and iterative site-specific mutagenesis, the best quadruple mutant N292H/K524S/A627L/E1121W (M3) was successfully obtained. In comparison to the wildtype SrCAR, M3 demonstrated a 4.2-fold increase in catalytic efficiency (kcat/Km), and its half-life (t1/2) was enhanced by 3.8 times up to 385.08 minutes at 40 °C. In silico docking and molecular dynamics simulation provided insights into the improved activity and stability. In the subsequent preparative-scale reaction with 100 mM (16.8 g L−1) vanillic acid, the whole cell catalysis utilizing M3 produced 10.15 g·L−1 of vanillin and 1.11 g·L−1 of vanillyl alcohol, respectively. This work demonstrates a dual improvement in the activity and thermal stability of SrCAR, thereby potentially facilitating the application of carboxylic acid reductase in the biosynthesis of vanillin.

A content analysis of the frequency of fat talk in Walt Disney animation films (1937–2021)

PurposePrevious research demonstrates a consistent association between the media and body and eating related issues in children. Recent research has highlighted a role for “fat talk” to describe discourses around body size and food. One key source of media information is Disney animation films, yet to date no research study has explored the verbal content of this genre.Design/methodology/approachThe present study used a content analysis to examine fat talk in Disney animation films (1937–2021; n = 53) with a focus on the frequency of fat talk, changes over time and differences between the genders and heroic statuses of the givers and receivers of fat talk. Fat talk was defined as relating to both body size and food and could be either positive or negative.FindingsResults revealed that there was more negative than positive fat talk per film; no significant changes over time; males were the givers of significantly more positive and negative fat talk than females and were also the receivers of more negative fat talk; good characters were the givers and receivers of more positive and negative fat talk and more self-directed negative fat talk than bad characters.Practical implicationsThe results are discussed in terms of possible legislation and parenting interventions to minimise the harm of this genre on young children.Originality/valueDisney animation films may not be as benign as often thought.

Therapeutic potential and roles of dietary seaweeds in food: A systematic review

Food security is a significant global concern as a result of the burden that the fast-expanding global population has placed on finite resources, such as arable land for farming. Additionally, the hunt for more nutritious food alternatives has been prompted by a growing understanding of health, nutrition, and diet. Seaweeds are simple-to-grow aquatic plants that are underused for food and medicine. Recent studies have focused on gaining access to and using these readily available natural resources for nutrition and medicinal objectives. This review systematically evaluated trends of recent research on seaweed, for therapeutic possibilities and product development. After examining several documents, this analysis discovered that seaweeds are incredibly beneficial algae for both nutrition and medicine, and may be further explored in innovative food products, in meeting the increasing global need for food.

MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4

Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases.

The correlation between iodine and metabolism: a review.

Iodine is involved in the synthesis of thyroid hormones and plays a crucial role in human life. Both iodine deficiency and excess are common issues in certain populations. Iodine also has extrathyroidal effects on organs that can uptake it independently of thyroid hormones. Recently, multiple clinical studies have shown a connection between iodine intake and metabolic disorders, such as metabolic syndrome, obesity, diabetes, hypertension, and dyslipidemia. However, the results of these studies have been inconsistent, and the mechanisms behind these associations are still not well understood. Therefore, in this review, we aim to examine the recent research progress regarding the relationship between iodine and metabolic disorders, along with the relevant mechanisms.

Smart Wheel Chair for Specially Abled People

Numerous people experience either temporary or permanent disability as a result of illnesses or accidents. When one's mobility is difficult or impossible, using a wheelchair becomes essential. Wheelchairs that are manually or electrically operated sufficiently satisfy the requirements of people with mild to moderate disabilities, enabling them to drive the wheelchair on their own. However, using a wheelchair independently becomes difficult or impossible in cases of severe handicap. To overcome these obstacles, wheelchair technology researchers are working to create intelligent wheelchair solutions. This paper reviews recent research on smart wheelchair systems with the goal of evaluating current technology and identifying future areas of research.

How the Intensity of Preference for Ideological Judges Influences Court Support

Recent research shows that many people support courts based on their ideological congruence with those courts and their decisions. But people likely hold varying degrees of intensity in their preferences for judges who will implement conservative or liberal policy. We suspect that court support is a function of that intensity. Our results agree. Court support turns on the intensity with which people prefer conservative, moderate, or liberal judges. In fact, accounting for the strength with which people prefer ideological judges explains more of their support for courts than some existing approaches.

Nothing less than a creative triumph: a study of children admitted to hospital for serious somatic illness or injury and their experience of art therapy.

Hospitalization can be an extremely distressing experience for seriously ill and injured children. Art therapy has a well-established clinical history, and recent research has begun to demonstrate its effectiveness in somatic pediatric wards. Descriptive and statistical research indicates that art therapy can alleviate anxiety and fear, improve mood, and enhance communication among children, parents, and healthcare professionals. This study aims to enhance our understanding of the specific elements of art therapy that facilitate a connection with the healthier aspects of the self. A total of 12 hospitalized children, aged 4-12, participated in an art therapy session led by a certified art therapist. Verbalizations during the sessions were recorded, and subsequent observations were synchronized with verbatim transcriptions of audio recordings. A reflexive thematic analysis was conducted to identify relevant patterns of meaning. The study identified four significant dimensions of the children's experiences during art therapy: (1) The child feels safe, (2) The child becomes a competent artist, bursting with creativity, (3) The healthy child emerges, and (4) The child achieves something beyond its limits - a triumph. The active ingredients contributing to effective art therapy include the stimulation of creativity, guided art-making with scaffolding support, task variation, granting children control over the artistic process, encouragement of free expression, and the display of positive regard. This study also delves into the therapeutic alliance, emphasizing its role in facilitating children's learning, self-expression, concentration, and the creation of work they take pride in. Additionally, certain psychotherapy-like interactions, such as control-mastery dynamics, were observed. Nevertheless, more extensive research with larger sample sizes is required to draw broader conclusions.

Correlates of post-traumatic growth among persons bereaved from cancer: A systematic review and meta-analysis.

Recent research identified that cancer bereavement can lead to post-traumatic growth (PTG). Although PTG and its correlates are well explored in cancer patients and survivors, persons bereaved from cancer have received scant attention. Therefore, the present review attempts to identify the correlates of PTG among persons bereaved from cancer. A systematic search in PubMed, Web of Science, APA PsycNet, Science Direct, Scopus, and Wiley was conducted to identify quantitative studies published in English, resulting in 12 eligible reports being included in the final analysis. JBI critical checklists were employed to appraise the risk of bias. The review identified 17 correlates, which were classified into four categories: demographic factors (age, gender, religious status, level of education), loss-related factors (time since death, quality of death, prolonged grief symptoms), interpersonal factors (relationship to the deceased, social support, attachment style, bereavement behaviours) and intrapersonal factors (resilience, coping, rumination, benevolence, meaningfulness, self-worth). Random effects meta-analyses on six correlates revealed correlation coefficients of age = -0.02 (95% CI: -0.35-0.31), gender = 0.27 (95% CI: 0.08-0.45), time since death = 0.09 (95% CI: -0.02-0.20), quality of death = 0.29 (95% CI: -0.01-0.54), prolonged grief symptoms = 0.22 (95% CI: 0.08-0.35) and relationship to the deceased = 0.13 (95% CI: -0.03-0.29). Fixed effects meta-analysis was performed for social support (r = 0.13, 95% CI: 0.04-0.21). However, PTG was found to be significantly associated with gender, prolonged grief symptoms, and social support. Very few studies examined PTG among persons bereaved from cancer, highlighting the need for increased attention, understanding, and conceptualisation of PTG in the population.

Foreign Policy as Compensation: Why Brexit Became a Foreign and Security Policy Issue

Abstract Exogenous reform demands can put leaders in a tight spot where change runs up against structural impediments. Yet, where asymmetries in reform costs occur across domains, leaders can seek to re-frame the impetus of change from one domain to another. Such compensatory behavior is commonplace but is not adequately captured by existing research on linkage politics, forum shopping, or diversionary conflict. This article develops the concept of compensatory foreign policy, whereby leaders use foreign policy change to compensate for unviable economic reforms when they have greater capacity and choice in the former domain. Empirically, we use elite interviews to reconstruct the politics of security policy in the post-Brexit United Kingdom, showing how party leaders focused on foreign policy change when beneficial economic arrangements were precluded. Our argument contributes to recent research on linkage politics by demonstrating the conditions under which leaders seek foreign policy reforms to compensate for economic weakness.

Recent advancements in the role of histone acetylation dynamics to improve stress responses in plants.

In eukaryotes, transcriptional regulation is determined by the DNA sequence and is facilitated through sophisticated and complex chromatin alterations and histone remodelling. Recent research has shown that the histone acetylation dynamic, an intermittent and reversible substitution, constitutes a prerequisite for chromatin modification. These changes in chromatin structure modulate genome-wide and specific changes in response to external and internal cues like cell differentiation, development, growth, light temperature, and biotic stresses. Histone acetylation dynamics also control the cell cycle. HATs and HDACs play a critical role in gene expression modulation during plant growth and response to environmental circumstances. It has been well established that HATs and HDACs interact with various distinct transcription factors and chromatin-remodelling proteins (CRPs) involved in the transcriptional regulation of several developmental processes. This review explores recent research on histone acyltransferases and histone deacetylases, mainly focusing on their involvement in plant biotic stress responses. Moreover, we also emphasized the research gaps that must be filled to fully understand the complete function of histone acetylation dynamics during biotic stress responses in plants. A thorough understanding of histone acetylation will make it possible to enhance tolerance against various kinds of stress and decrease yield losses in many crops.

Exploring the significance of microbiota metabolites in rheumatoid arthritis: uncovering their contribution from disease development to biomarker potential.

Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota-derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine-N-oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined.

Hsa_circ_0008360 promotes high glucose-induced damage in HK-2 cells via miR-346/WNT2B axis.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of DN, but the mechanism isstill indistinct. In this work, we explored the roles of hsa_circ_0008360 in DN. The levels of hsa_circ_0008360, microRNA-346 (miR-346) and Winglesstype family member 2B (WNT2B) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in DN tissues and HK2 cells. Meanwhile, the protein level of WNT2B was quantified by Western blot analysis. Besides, the function of cells was examined by Cell Counting Kit-8 (CCK8) assay, flow cytometry assay, western blot, and ELISA kit. Furthermore, the interplay between miR-346 and hsa_circ_0008360 or WNT2B was detected by dual-luciferase reporter assay. The levels of hsa_circ_0008360 and WNT2B were increased, and the miR-346 level was decreased in the serum of DN patients and HG-treated HK2 cells. For functional analysis, hsa_circ_0008360 deficiency promoted cell viability, inhibits cell apoptosis, inflammatory response, and the synthesis of related fibrotic proteins in HG-treated HK2 cells. Moreover, overexpression of miR-346 induced the proliferation and inhibit apoptosis of HG-induced HK2 cells by inhibiting WNT2B expression. In mechanism, hsa_circ_0008360 acted as a miR-346 sponge to regulate the level of WNT2B. Hsa_circ_0008360 can regulate miR-346/WNT2B axis in HG-induced HK2 cells, providing an underlying targeted therapy for DN patients.

Rebalance Your Investment Portfolio Periodically: Mantra or Myth?

Rebalance Your Investment Portfolio Periodically: Mantra or Myth?

The Interplay of Mitochondrial Bioenergetics and Dopamine Agonists as an Effective Disease-Modifying Therapy for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurological ailment with a slower rate of advancement that is more common in older adults. The biggest risk factor for PD is getting older, and those over 60 have an exponentially higher incidence of this condition. The failure of the mitochondrial electron chain, changes in the dynamics of the mitochondria, and abnormalities in calcium and ion homeostasis are all symptoms of Parkinson's disease (PD). Increased mitochondrial reactive oxygen species (mROS) and an energy deficit are linked to these alterations. Levodopa (L-DOPA) is a medication that is typically used to treat most PD patients, but because of its negative effects, additional medications have been created utilizing L-DOPA as the parent molecule. Ergot and non-ergot derivatives make up most PD medications. PD is successfully managed with the use of dopamine agonists (DA). To get around the motor issues produced by L-DOPA, these dopamine derivatives can directly excite DA receptors in the postsynaptic membrane. In the past 10years, two non-ergoline DA with strong binding properties for the dopamine D2 receptor (D2R) and a preference for the dopamine D3 receptor (D3R) subtype, ropinirole, and pramipexole (PPx) have been developed for the treatment of PD. This review covers the most recent research on the efficacy and safety of non-ergot drugs like ropinirole and PPx as supplementary therapy to DOPA for the treatment of PD.

Self-Defense Mechanism in Rice to Salinity: Proline

The increasing global population and climate change threaten food security, with the need for sustenance expected to rise by 85% by 2050. Rice, a crucial staple food for over 50% of the global population, is a major source of calories in underdeveloped and developing countries. However, by the end of the century, over 30% of rice fields will become saline due to soil salinity caused by earthquakes, tsunamis, and rising sea levels. Plants have developed strategies to deal with salt stress, such as ion homeostasis, antioxidant defense mechanisms, and morphological adaptations. Proline, an endogenous osmolyte, is the predominant endogenous osmolyte that accumulates in response to salinity, and its overexpression in rice plants has been observed to increase plant salinity tolerance. Exogenously applied proline has been shown to improve plant salt tolerance by reducing the destructive effect of salinity. Recent research has focused on ionic toxicity, nitrogen fixation, and gene expression related to salt tolerance. Exogenous proline has been shown to improve water potential and leaf content, restoring water usage efficiency. It can also ease growth inhibition in salt-sensitive plants. Exogenously applied proline increases antioxidant activities and enhances plant salinity tolerance. This review examines the role and processes of proline in rice plants under salt stress and its relationship with other tolerance mechanisms.

Who's being elitist? A debate about the enregisterment of Singlish

Abstract This article is a rejoinder to Lee (2023) who makes certain claims about the enregisterment of Singlish via a case study of Spiaking Singlish. In challenging Lee's key claim that Spiaking Singlish deploys a form of elitist language, I argue that the Singlish features in the book need not demand a solely ludic reading and actually draw from everyday practices. Accordingly, enregisterment ought to be understood as a diachronic and evolving process in the vein of Butler's (1999) notion of sedimentation. Moreover, Lee's characterization of the ‘monolectal Singlish user’ is classist and reductionist, unsupported by recent research and census data. Consequently, Spiaking Singlish need not be seen as an elitist work, but as contributing to ever-changing attitudes towards Singlish in the public sphere. This article is an alternative iteration to Lee's (2023) that has implications for the way we understand enregisterment in Singapore and choose to represent it as a process. (Enregisterment, Singlish, Singapore, sociolinguistics, language ideological debates)*

In service of disruption: examining mediators of White racial identity through inservice professional development addressing race and racism

ABSTRACT Research on professional development (PD) with practicing White teachers has traditionally focused on shifting White teachers’ attitudes, whereas more recent research has explored the role of emotions in White teachers’ engagement in such learning. Leveraging theory on culturally disruptive pedagogy and a qualitative phenomenological approach, this article analyses the experiences of a group of White educators across a suburban Mid-Atlantic district, asking, what common elements are associated with ‘disruptions’ White educators may experience in PD addressing race and racism? Building on previous research calling attention to the complex, multifaceted nature of White cultural conditioning and related processes of ‘unlearning’, cognitive, emotional, spatial, and embodied mediating elements are documented and analysed. Implications for future research and PD design and facilitation are discussed.