Lingering Questions Research Articles

Advances in functional studies of plant MYC transcription factors.

Myelocytomatosis (MYC) transcription factors (TFs) belong to the basic helix-loop-helix (bHLH) family in plants and play a central role in governing a wide range of physiological processes. These processes encompass plant growth, development, adaptation to biotic and abiotic stresses, as well as secondary metabolism. In recent decades, significant strides have been made in comprehending the multifaceted regulatory functions of MYCs. This advancement has been achieved through the cloning of MYCs and the characterization of plants with MYC deficiencies or overexpression, employing comprehensive genome-wide 'omics' and protein-protein interaction technologies. MYCs act as pivotal components in integrating signals from various phytohormones' transcriptional regulators to orchestrate genome-wide transcriptional reprogramming. In this review, we have compiled current research on the role of MYCs as molecular switches that modulate signal transduction pathways mediated by phytohormones and phytochromes. This comprehensive overview allows us to address lingering questions regarding the interplay of signals in response to environmental cues and developmental shift. It also sheds light on the potential implications for enhancing plant resistance to diverse biotic and abiotic stresses through genetic improvements achieved by plant breeding and synthetic biology efforts.

IgE and non-IgE food allergy: A review of immunological mechanisms.

Food allergic (FA) conditions have been classified as immunoglobulin E (IgE) and non-IgE-mediated reactions that affect as many as 8% of young children and 2% of adults in Western countries, and their prevalence seems to be rising. Although the immunologic basis of IgE-mediated FA is well established, the mechanisms that govern non-IgE-mediated FA are not well understood and are marked by a paucity of comprehensive insights. The purpose of the present report is to examine the current classification and epidemiology of non-IgE-mediated FA, the latest immunologic mechanisms that underlie the three most commonly cited non-IgE FA conditions, viz., eosinophilic esophagitis, food protein-induced enterocolitis, and food protein-induced allergic proctocolitis, and explore what allergist/immunologists in practice should be aware of with regard to the condition. An extensive research was conducted in medical literature data bases by applying terms such as FA, non-IgE allergy, tolerance, unresponsiveness, cytokines, CD4+ T helper cell pathways, and key cytokine pathways involved in FA. Current evidence now supports the view that immune dysregulation and cytokine-induced inflammation are the fundamental bases for both IgE- and non-IgE-mediated FA. The existing non-IgE-related FA literature is mostly characterized by a relative dearth of mechanistic information in contrast to IgE-mediated FA, in which the immunologic underpinnings as a T helper type 2 directed entity are well established. Although the need for future methodologic research and adherence to rigorous scientific protocols is essential, it is also necessary to acknowledge past contributions that have given much to our understanding of the condition. In the present report, a novel signature cytokine-based classification of IgE-mediated and non-IgE-mediated allergy is proposed that may offer a novel template for future research in the field of non-IgE-mediated FA. The present report provides an overview of the current classification and frequency of IgE- and non-IgE-mediated FAs, and offers insights and potential solutions to address lingering questions, particularly when concerning the latest immunologic mechanisms that underlie the pathogenesis of non-IgE-mediated FA. Although some progress has been made in recent years toward making diagnostic and treatment options available for these conditions, there still remain many lingering questions and concerns to be addressed, which can be fully understood by future research.

SARS-CoV-2 immunity in animal models.

The COVID-19 pandemic, which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide health crisis due to its transmissibility. SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals. These complications encompass symptoms such as coughing, respiratory distress, fever, infectious shock, acute respiratory distress syndrome (ARDS), and even multiple-organ failure. Animal models serve as crucial tools for investigating pathogenic mechanisms, immune responses, immune escape mechanisms, antiviral drug development, and vaccines against SARS-CoV-2. Currently, various animal models for SARS-CoV-2 infection, such as nonhuman primates (NHPs), ferrets, hamsters, and many different mouse models, have been developed. Each model possesses distinctive features and applications. In this review, we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection, as well as the corresponding immune responses and applications of these models. A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients. Finally, we highlighted the current gaps in related research between animal model studies and clinical investigations, underscoring lingering scientific questions that demand further clarification.

EEG-based study of design creativity: a review on research design, experiments, and analysis.

Brain dynamics associated with design creativity tasks are largely unexplored. Despite significant strides, there is a limited understanding of the brain-behavior during design creation tasks. The objective of this paper is to review the concepts of creativity and design creativity as well as their differences, and to explore the brain dynamics associated with design creativity tasks using electroencephalography (EEG) as a neuroimaging tool. The paper aims to provide essential insights for future researchers in the field of design creativity neurocognition. It seeks to examine fundamental studies, present key findings, and initiate a discussion on associated brain dynamics. The review employs thematic analysis and a forward and backward snowball search methodology with specific inclusion and exclusion criteria to select relevant studies. This search strategy ensured a comprehensive review focused on EEG-based creativity and design creativity experiments. Different components of those experiments such as participants, psychometrics, experiment design, and creativity tasks, are reviewed and then discussed. The review identifies that while some studies have converged on specific findings regarding EEG alpha band activity in creativity experiments, there remain inconsistencies in the literature. The paper underscores the need for further research to unravel the interplays between these cognitive processes. This comprehensive review serves as a valuable resource for readers seeking an understanding of current literature, principal discoveries, and areas where knowledge remains incomplete. It highlights both positive and foundational aspects, identifies gaps, and poses lingering questions to guide future research endeavors.

An unstructured proteasome inhibitor comes into focus

The inhibitory mechanism of an intrinsically disordered proteasome inhibitor identified over 30years ago has finally been revealed by cryo-electron microscopy by Hsu etal. in a recent report in the Journal of Biological Chemistry. The structure, coupled with biochemical and cell-based experiments, resolves lingering questions about how the inhibitor achieves multisite inhibition of proteasomal protease activity, while raising several exciting new questions on the nature of proteasome subpopulations in the process.

Lessons from discovery of true ADAR RNA editing sites in a human cell line

BackgroundConversion or editing of adenosine (A) into inosine (I) catalyzed by specialized cellular enzymes represents one of the most common post-transcriptional RNA modifications with emerging connection to disease. A-to-I conversions can happen at specific sites and lead to increase in proteome diversity and changes in RNA stability, splicing, and regulation. Such sites can be detected as adenine-to-guanine sequence changes by next-generation RNA sequencing which resulted in millions reported sites from multiple genome-wide surveys. Nonetheless, the lack of extensive independent validation in such endeavors, which is critical considering the relatively high error rate of next-generation sequencing, leads to lingering questions about the validity of the current compendiums of the editing sites and conclusions based on them.ResultsStrikingly, we found that the current analytical methods suffer from very high false positive rates and that a significant fraction of sites in the public databases cannot be validated. In this work, we present potential solutions to these problems and provide a comprehensive and extensively validated list of A-to-I editing sites in a human cancer cell line. Our findings demonstrate that most of true A-to-I editing sites in a human cancer cell line are located in the non-coding transcripts, the so-called RNA 'dark matter'. On the other hand, many ADAR editing events occurring in exons of human protein-coding mRNAs, including those that can recode the transcriptome, represent false positives and need to be interpreted with caution. Nonetheless, yet undiscovered authentic ADAR sites that increase the diversity of human proteome exist and warrant further identification.ConclusionsAccurate identification of human ADAR sites remains a challenging problem, particularly for the sites in exons of protein-coding mRNAs. As a result, genome-wide surveys of ADAR editome must still be accompanied by extensive Sanger validation efforts. However, given the vast number of unknown human ADAR sites, there is a need for further developments of the analytical techniques, potentially those that are based on deep learning solutions, in order to provide a quick and reliable identification of the editome in any sample.

A coating strategy on titanium implants with enhanced photodynamic therapy and CO-based gas therapy for bacterial killing and inflammation regulation

Antimicrobial photodynamic therapy (aPDT) has been considered a noninvasive and effective modality against the bacterial infection of peri‑implantitis, especially the aPDT triggered by near-infrared (NIR) light due to the large penetration depth in tissue. However, the complexity of hypoxia microenvironments and the distance of aPDT sterilization still pose challenges before realizing the aPDT clinical application. Due to the long lifespan and transmission distance of therapeutic gas molecules, we design a multi-functional gas generator that combines aPDT as well as O2 and CO gas release function, which can solve the problem of hypoxia (O2) in PDT and the problem of inflammation regulation (CO) in the distal part of peri‑implant inflammation under near-infrared (NIR) irradiation. In the composite nanoplatform that spin-coated on the surface of titanium implants, up-conversion nanoparticles (UCNPs) were involved in converting the NIR to visible, which further excites the partially oxidized stannic sulfide (SnS2), realizing the therapeutic gas release. Indocyanine green (ICG) was further integrated to enhance the aPDT performance (Ti-U@SnS2/I). Therefore, reactive oxygen species (ROS), CO, and O2 can be controllably administered via a composite nano-platform mediated by a single NIR light (808 nm). This implant surface modification strategy could achieve great self-enhancement antibacterial effectiveness and regulate the lingering questions, such as relieving the anoxic microenvironment and reaching deep infection sites, providing a viable antibiotic-free technique to combat peri‑implantitis.

Nina Rattner Gelbart. Minerva’s French Sisters: Women of Science in Enlightenment France.

Nina Rattner Gelbart’s important new book, Minerva’s French Sisters: Women of Science in Enlightenment France, is a collective biography of six female scientists whose contributions to mathematics, astronomy, botany, epistemology, anatomy, and medical education were pathbreaking. While these women were celebrated in their own time, much of their work and correspondence has since been lost. Later writers downplayed their accomplishments, obfuscating their importance to the history of science. The brilliance of Gelbart’s book lies in her reconstruction of their histories from what male contemporaries said about them—in letters, reviews, eulogies, and obituaries—and from snippets of information found in a wide range of other sources from wills to paintings to ship logs. She traces the development of each woman as a scientist, explains her scientific accomplishments and their meaning, and charts her engagement with male scientists and the public. In experimenting with the biographical format, Gelbart follows each chapter with a letter to its subject; she asks lingering questions, updates the subject on her neighborhood and legacy, and bears witness to her accomplishments and struggles.

Simulated effects of cover crops with no-tillage on soil and crop productivity in rainfed semi-arid cotton production systems

Cover cropping and no-tillage (NT) practices are promoted for soil health and environmental benefits. However, producing enough quantity of biomass to meet expected benefits can be a challenge in semi-arid cropping systems where water resources are limited, and producers have lingering questions regarding cover crop selection, termination timings, water use, and their subsequent effect on cash crop. The objective of this study was to assess the impacts of cover crops with NT on soil and crop productivity in a rainfed, continuous cotton (Gossypium hirsutum L.) system using the Denitrification Decomposition (DNDC) model. Treatments included: (a) conventional till (CT); (b) NT, and NT with the following cover crops: (c) Austrian winter pea (Pisum sativum L.) (Pea); (d) crimson clover (Trifolium incarnatum L.) (Clover); (e) hairy vetch (Vicia villosa L.) (Vetch); (f) a multi-species mixture (Mixture); and (g) winter wheat (Triticum aestivum L.) (Wheat). The DNDC model adequately simulated the seed cotton yield and cover crop biomass during calibration (root mean square error (RMSE) = 200 and 398 kg ha−1, respectively) and validation (RMSE = 277 and 270 kg ha−1, respectively). Stocks of soil organic carbon (SOC) and total nitrogen (TN) were simulated with Nash–Sutcliffe efficiency (NSE) of 0.91 and 0.78 during calibration, and with NSE of 0.88 and 0.75, respectively during validation. Long-term simulations revealed: (1) Vetch and Pea produced greater biomass and hence highest SOC and TN contents, which was followed by Mixture, Wheat, and Clover; (2) cotton yield in cover crop treatments was no different to that in non-cover crop treatments when cover crop was terminated about six weeks prior to cotton planting; (3) later termination of cover crops can result in greater cotton yield loss due to soil water depletion by cover crops. Overall, this study highlights the potential of conservation practices, such as cover crops and NT to improve soil health without significant loss in cotton yields.

Still Jammed! Lingering Questions About the Statutory Unconscionability Doctrine Post Stubbings v Jams 2 Pty Ltd (2022) 399 ALR 409

The High Court of Australia recently delivered its highly anticipated judgment in Stubbings v Jams 2 Pty Ltd (2022) 399 ALR 409 (‘Stubbings (HCA)’). The case represents the most recent examination of the unsettled statutory doctrine of unconscionability in the land’s highest judicial forum. Regrettably, the High Court spurned the opportunity to clarify several lingering questions that continue to plague the doctrine. These questions concern matters ranging from the proper distinction between the various unconscionability provisions in the consumer law to the requirements needed under each. This article extrapolates what it can from Stubbings (HCA) and other leading cases to try and add clarity to the frequently litigated but poorly understood statutory unconscionability doctrine.

Racial discrimination predicts depressive symptoms throughout adolescence among Black youth.

Experiences of racial discrimination are common among Black youth and predict worse mental health cross-sectionally and over time. Additional research is needed to address lingering questions regarding the direction of effect(s) underlying these patterns, differences in the magnitude of effects across adolescence, and gender differences. To address these gaps, the current study tested bidirectional linkages between racial discrimination and depressive symptoms at the between- (interpersonal) and within- (intrapersonal) level using 4 waves of data from 889 Black youth (54% female) from Georgia and Iowa. Participants reported experiences of racial discrimination and depressive symptoms at ages 10.6 years (Wave 1), 12.5 years (Wave 2), 15.7 years (Wave 3), and 18.8 years (Wave 4). The cross-lagged panel model (CLPM) was used to examine between-person associations over time, and the random intercept cross-lagged panel model (RI-CLPM) was used to examine within-person associations over time. Results were consistent across models, revealing significant concurrent associations between racial discrimination and depressive symptoms, significant lagged effects from racial discrimination to depressive symptoms, and no significant lagged effects from depressive symptoms to racial discrimination. Effects did not differ across adolescence, and there were few gender differences in the degree of association between racial discrimination and depressive symptoms. Findings provide rigorous evidence that experiencing greater racial discrimination is associated with increases in depressive symptoms throughout adolescence and add to a growing body of work showing that racial discrimination can undermine mental health and well-being among Black youth. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Where is the When of Creativity?: Specifying the Temporal Dimension of the Four Cs of Creativity

Creativity researchers typically focus on the who, what, why, where, and how of creativity. A noticeable omission is when. The when is not completely ignored in the field; it surfaces in developmental and evolutionary perspectives, the study of eminent creators, and other avenues of scholarship. In this paper, we assert that for the concept of when to be fully addressed researchers need to more actively consider the past, present, and future and how they interact. More specifically, we propose an expanded way of thinking about the when of creativity by introducing a temporal dimension to the definition of creativity. Our definition offers a broader lens for researchers to consider the temporal dimensions of originality, meaningfulness, and impact of creativity. After introducing our definition and describing its unique features, we discuss how researchers can use our definition to trace creative phenomena across a full temporal trajectory and thereby provide more nuanced and dynamic representation of how the features of creativity change across time and contexts. Finally, we apply this temporal definition to the Four Cs Model of Creativity to illustrate how considering the when can help resolve lingering questions about this perspective.

Biomimetic antimicrobial polymers-Design, characterization, antimicrobial, and novel applications.

Biomimetic antimicrobial polymers have been an area of great interest as the need for novel antimicrobial compounds grows due to the development of resistance. These polymers were designed and developed to mimic naturally occurring antimicrobial peptides in both physicochemical composition and mechanism of action. These antimicrobial peptide mimetic polymers have been extensively investigated using chemical, biophysical, microbiological, and computational approaches to gain a deeper understanding of the molecular interactions that drive function. These studies have helped inform SARs, mechanism of action, and general physicochemical factors that influence the activity and properties of antimicrobial polymers. However, there are still lingering questions in this field regarding 3D structural patterning, bioavailability, and applicability to alternative targets. In this review, we present a perspective on the development and characterization of several antimicrobial polymers and discuss novel applications of these molecules emerging in the field. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Long COVID: defining the role of rheumatology in care and research.

The global pandemic of COVID-19 has had an impact on the profession of rheumatology from many perspectives, including its effects on our patients with immune-mediated conditions and immunocompromised states, the disruption of care pathways, and beyond. There also are lingering questions about how the next phase of the pandemic will evolve, with the continuing emergence of new viral variants posing a continuing threat to our patients. Beyond these formidable challenges is the uncertainty around the long-term effects of COVID-19—referred to as long COVID among other names—in the rheumatology patient population, and the role of the rheumatology practitioner in care of and research among this population.

Cytokine and metabolic regulation of adipose tissue Tregs.

Since their discovery over a decade ago, much has been learned regarding the importance and function of visceral adipose tissue (VAT)-resident regulatory T cells (Tregs). VAT Tregs play a critical role in controlling VAT inflammation and alleviating metabolic disease. However, this population is disrupted in obesity which exacerbates VAT inflammation and metabolic abnormalities. Therefore, understanding the factors governing the accumulation and maintenance of VAT Tregs, both at steady state and under disease conditions, is crucial for identifying the mechanisms underlying obesity-associated metabolic disease and developing novel therapies. Expansion and maintenance of the VAT Treg compartment is strongly influenced by factors in the local tissue microenvironment, including cytokines, T-cell receptor ligands, hormones, and various metabolites. This mini-review will primarily focus on recent advances in our understandings regarding the regulation of mouse epididymal VAT (eVAT) Tregs, which are the most thoroughly characterized VAT Treg population, by tissue microenvironmental factors and cellular metabolic processes. We will also briefly discuss the limited knowledge available regarding the regulation of mouse ovarian VAT (oVAT) Tregs and human omental VAT Tregs, highlight some lingering questions, and provide a prospective view on where the field is heading.

The Shortest Stories and the Power of Parental Presence

In this narrative medicine essay, a pediatrician describes his lingering questions about the care his daughter received during her very brief life while he was barred from operating room and compares it to being present when another daughter experienced a stressful birth.

A qualitative study examining the impact of multidrug-resistant organism (MDRO) carriage on the daily lives of carriers and parents of carriers with experiences of hospital precautionary measures

BackgroundMultidrug-resistant organism (MDRO) carriage may have an adverse impact on the quality of life of carriers, in particular those who have experienced hospital precautionary measures. This study aims to gain a deeper understanding of how MDRO carriage has affected the daily lives of carriers with these experiences.MethodsThis was a qualitative study based on 15 semi-structured interviews with MDRO carriers or parents of carriers, which were analysed by thematic analysis.ResultsThree main themes were identified: (1) Feeling dirty and unworthy portrays the feelings that MDRO carriers often expressed and how these were related to the language usage describing the MDRO, the perceived avoidance by staff and those in their personal networks, and the effects of the precautionary measures implemented in the hospital. (2) MDROs are invisible, but impact is visible covers how the microbe, despite its apparent invisibility, still impacted carriers in their physical and psychological health. MDRO carriage disrupted their lives, by affecting their other unrelated medical conditions at times and by causing varying levels of fear for their own and others’ health. (3) Carrying the burden on one’s own shoulders describes the lingering questions, uncertainties and confusion that carriers continued to live with and the perceived burden and responsibility that lay on their own shoulders with respect to carrying and preventing the transmission of the MDRO.ConclusionsMDRO carriage can negatively influence the quality of people’s lives in various ways. Improved support and sensitivity from health care providers (HCPs) are needed to address feelings of unworthiness among MDRO carriers and the fears that many experience. Clearer information and guidelines are also needed from HCPs to address the many questions and uncertainties that MDRO carriers face outside of the hospital in their daily lives.

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Do Advisories, Warnings, or Color Coding Matter to Risk Perception and Precautionary Decisions?

Abstract There are lingering questions about the effectiveness of the watch, warning, and advisory system (WWA) used to convey weather threats in the United States. Recently there has been a shift toward alternative communication strategies such as the impact-based forecast. The study reported here compared users’ interpretation of a color-coded impact-based prototype designed for email briefings, to a legacy WWA format. Participants, including emergency managers and members of the public, saw a weather briefing and rated event likelihood, severity, damage, and population affected. Then they recommended emergency response actions. Each briefing described the severity of the weather event and the degree of impact on population and property. In one condition a color-coded impacts scale was added to the text description. In another, an advisory and/or warning was added to the text description. These were compared with the text-only control. Both emergency managers and members of the public provided higher ratings for event likelihood, severity, damage, and population affected and recommended a greater response for higher impact levels regardless of format. For both groups, the color-coded format decreased ratings for lower-impact events. Among members of the public, the color-coded format also led to increases for many ratings and greater response at higher levels relative to the other two conditions. However, the highest ratings among members of the public were in the WWA condition. Somewhat surprisingly, the only effect of the WWA format on emergency managers was to reduce action recommendations, probably because of the inclusion of the “advisory” in some briefings.

Adult Stepchildren’s Uncertainty Management in Later Life Stepfamilies: Illuminating the Role of Context, Intentionality, Collaboration, and Information Implications

ABSTRACT Increasing divorce and remarriage rates among middle and older aged adults has resulted in an uptick of later life stepfamilies (LLSF). Despite these growing numbers, research often focuses on stepfamily development in adolescence, leaving lingering questions about how adult stepchildren navigate this transition, including grappling with uncertainties. Guided by uncertainty management theory, we conducted in-depth, semi-structured interviews with 26 adult stepchildren (ASC). Thematic analysis revealed four primary information acquisition strategies: (a) strategic information seeking, (b) strategic information avoiding, (c) incidental information acquisition, and (d) information ambivalence. Further, ASC’s information acquisition tactics are informed by contextual factors germane to LLSFs (e.g., proximity), vary by degree of intentionally, are collaborative in nature, and are connected to relational implications. Together, our findings result in a conceptual model of LLSF uncertainty management that extends understanding of uncertainty management within family systems.