Recent Findings Research Articles

Genomic insights into Verticillium: a review of progress in the genomics era

Genomics has emerged as a great tool in enhancing our understanding of the biology of Verticillium species and their interactions with the host plants. Through different genomic approaches, researchers have gained insights into genes, pathways and virulence factors that play crucial roles in both Verticillium pathogenesis and the defense responses of their host organisms. This review emphasizes the significance of genomics in uncovering the mechanisms that underlie pathogenicity, virulence, and host resistance in Verticillium fungi. Our goal is to summarize recent discoveries in Verticillium research highlighting progress made in comprehending the biology and interactions of Verticillium fungi. The integration of genomics into Verticillium studies has the potential to open avenues for developing strategies to control diseases and produce crop varieties resistant to verticillium, thereby offering sustainable solutions for enhancing agricultural productivity.

Virome Characterization of Native Wild-Rice Plants Discovers a Novel Pathogenic Rice Polerovirus With World-Wide Circulation.

Pandemics originating from zoonotic viruses have posed significant threats to human health and agriculture. Recent discoveries have revealed that wild-rice plants also harbour viral pathogens capable of severely impacting rice production, a cornerstone food crop. In this study, we conducted virome analysis on ~1000 wild-rice individual colonies and discovered a novel single-strand positive-sense RNA virus prevalent in these plants. Through comprehensive genomic characterization and comparative sequence analysis, this virus was classified as a new species in the genus Polerovirus, designated Rice less tiller virus (RLTV). Our investigations elucidated that RLTV could be transmitted from wild rice to cultivated rice via a specific insect vector, the aphid Rhopalosiphum padi, causing less tiller disease symptoms in rice plants. We generated an infectious cDNA clone for RLTV and demonstrated systemic infection of rice cultivars and induction of severe disease symptoms following mechanical inoculation or stable genetic transformation. We further illustrated transmission of RLTV from stable transgenic lines to healthy rice plants by the aphid vector, leading to the development of disease symptoms. Notably, our database searches showed that RLTV and another polerovirus isolated from a wild plant species are widely circulating not only in wild rice but also cultivated rice around the world. Our findings provide strong evidence for a wild plant origin for rice viruses and underscore the imminent threat posed by aphid-transmitted rice Polerovirus to rice cultivar.

Discovery of Two New Eruptions of the Ultrashort Recurrence Time Nova M31N 2017-01e* *Based on observations obtained with the Hobby-Eberly Telescope (HET), which is a joint project of the University of Texas at Austin, the Pennsylvania State University, Ludwig-Maximillians-Universitaet Muenchen, and Georg-August Universitaet Goettingen. The HET is named in honor of its principal benefactors, William P. Hobby and Robert E.

We report the recent discovery of two new eruptions of the recurrent nova M31N 2017-01e in the Andromeda galaxy. The latest eruption, M31N 2024-08c, reached R = 17.8 on 2024 August 06.85 UT, ∼2 months earlier than predicted. In addition to this recent eruption, a search of archival Palomar Transient Factory data has revealed a previously unreported eruption on 2014 June 18.46 UT that reached a peak brightness of R ∼ 17.9 approximately a day later. The addition of these two eruption timings has allowed us to update the mean recurrence time of the nova. We find 〈T rec〉 = 924.0 ± 7.0 days (2.53 ± 0.02 yr), which is slightly shorter than our previous determination. Thus, M31N 2017-01e remains the nova with the second shortest recurrence time known, with only M31N 2008-12a being shorter. We also present a low-resolution spectrum of the likely quiescent counterpart of the nova, a ∼20.5 mag evolved B star displaying an ∼14.3 days photometric modulation.

Mitochondrial Function and Dysfunction in White Adipocytes and Therapeutic Implications.

For a long time, white adipocytes were thought to function as lipid storages due to the sizeable unilocular lipid droplet that occupies most of their space. However, recent discoveries have highlighted the critical role of white adipocytes in maintaining energy homeostasis and contributing to obesity and related metabolic diseases. These physiological and pathological functions depend heavily on the mitochondria that reside in white adipocytes. This article aims to provide an up-to-date overview of the recent research on the function and dysfunction of white adipocyte mitochondria. After briefly summarizing the fundamental aspects of mitochondrial biology, the article describes the protective role of functional mitochondria in white adipocyte and white adipose tissue health and various roles of dysfunctional mitochondria in unhealthy white adipocytes and obesity. Finally, the article emphasizes the importance of enhancing mitochondrial quantity and quality as a therapeutic avenue to correct mitochondrial dysfunction, promote white adipocyte browning, and ultimately improve obesity and its associated metabolic diseases. © 2024 American Physiological Society. Compr Physiol 14:5581-5640, 2024.

The ascorbate peroxidase–related protein: insights into its functioning in Chlamydomonas and Arabidopsis

We review the newly classified ascorbate peroxidase–related (APX-R) proteins, which do not use ascorbate as electron donor to scavenge H2O2. We summarize recent discoveries on the function and the characterization of the APX-R protein of the green unicellular alga Chlamydomonas reinhardtii and the land plant Arabidopsis thaliana. Additionally, we conduct in silico analyses on the conserved MxxM motif, present in most of the APX-R protein in different organisms, which is proposed to bind copper. Based on these analyses, we discuss the similarities between the APX-R and the class III peroxidases.

Revealing the mechanism of natural product-induced immunogenic cell death: opening a new chapter in tumor immunotherapy

This review underscores the role of natural products in inducing immunogenic cell death (ICD) as a key strategy in tumor immunotherapy. It reveals that natural products can activate ICD through multiple pathways—apoptosis, autophagy, pyroptosis, and necroptosis—leading to the release of danger-associated molecular patterns (DAMPs), dendritic cell activation, and improved antigen presentation, which together stimulate a potent anti-tumor immune response. The study also demonstrates the enhanced therapeutic potential of combining natural products with immune checkpoint inhibitors. With a focus on translating preclinical findings into clinical practice, this review consolidates recent discoveries and suggests future research paths, offering both theoretical insights and practical guidance for advancing cancer immunotherapy.

Immunologic aspects of asthma: from molecular mechanisms to disease pathophysiology and clinical translation

In the present review, we focused on recent translational and clinical discoveries in asthma immunology, facilitating phenotyping and stratified or personalized interventions for patients with this condition. The immune processes behind chronic inflammation in asthma exhibit marked heterogeneity, with diverse phenotypes defining discernible features and endotypes illuminating the underlying molecular mechanisms. In particular, two primary endotypes of asthma have been identified: “type 2-high,” characterized by increased eosinophil levels in the airways and sputum of patients, and “type 2-low,” distinguished by increased neutrophils or a pauci-granulocytic profile. Our review encompasses significant advances in both innate and adaptive immunities, with emphasis on the key cellular and molecular mediators, and delves into innovative biological and targeted therapies for all the asthma endotypes. Recognizing that the immunopathology of asthma is dynamic and continuous, exhibiting spatial and temporal variabilities, is the central theme of this review. This complexity is underscored through the innumerable interactions involved, rather than being driven by a single predominant factor. Integrated efforts to improve our understanding of the pathophysiological characteristics of asthma indicate a trend toward an approach based on disease biology, encompassing the combined examination of the clinical, cellular, and molecular dimensions of the disease to more accurately correlate clinical traits with specific disease mechanisms.

The emerging modulators of non-coding RNAs in diabetic wound healing

Diabetic wound healing is a complex physiological process often hindered by the underlying metabolic dysfunctions associated with diabetes. Despite existing treatments, there remains a critical need to explore innovative therapeutic strategies to improve patient outcomes. This article comprehensively examines the roles of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating key phases of the wound healing process: inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Through a deep review of current literature, we discuss recent discoveries of ncRNAs that have been shown to either promote or impair the wound healing process in diabetic wound healing, which were not covered in earlier reviews. This review highlights the specific mechanisms by which these ncRNAs impact cellular behaviors and pathways critical to each healing stage. Our findings indicate that understanding these recently identified ncRNAs provides new insights into their potential roles in diabetic wound healing, thereby contributing valuable knowledge for future research directions in this field.

Electrochemically Gated Frustrated Lewis Pair Chemistry in Electric Double Layer.

The recent discovery of frustrated Lewis pairs (FLPs) during the activation of small molecules has inspired extensive research across the full span of chemical science. Owing to the nature of weak interactions, it is experimentally challenging to directly observe and modulate FLP at the molecular scale. Here we design a boron cluster anion building block (B10H82-) and organic amine cations ([NR4]+, R= -CH3, -C2H5) as the FLP to prove the feasibility of controlling their interaction in the electric double layer (EDL) via an electrochemical strategy. In situ single-molecule electrical measurements and Raman monitoring of B10H82--[NR4]+ FLP formed at the positively charged Au(111) electrode surface, in contrast to the free-standing B10H82- near or below the potential of zero charge (PZC). Furthermore, this FLP chemistry leads to a shift in the local density of states of boron clusters towards the EF for enhancing electron transport, providing a new prototype of a reversible single-cluster switch that digitally switches upon controlling FLP chemistry in the electric double layer.

Electrochemically Gated Frustrated Lewis Pair Chemistry in Electric Double Layer

The recent discovery of frustrated Lewis pairs (FLPs) during the activation of small molecules has inspired extensive research across the full span of chemical science. Owing to the nature of weak interactions, it is experimentally challenging to directly observe and modulate FLP at the molecular scale. Here we design a boron cluster anion building block (B10H82‐) and organic amine cations ([NR4]+, R= ‐CH3, ‐C2H5) as the FLP to prove the feasibility of controlling their interaction in the electric double layer (EDL) via an electrochemical strategy. In situ single‐molecule electrical measurements and Raman monitoring of B10H82‐–[NR4]+ FLP formed at the positively charged Au(111) electrode surface, in contrast to the free‐standing B10H82‐ near or below the potential of zero charge (PZC). Furthermore, this FLP chemistry leads to a shift in the local density of states of boron clusters towards the EF for enhancing electron transport, providing a new prototype of a reversible single‐cluster switch that digitally switches upon controlling FLP chemistry in the electric double layer.

Emerging Nanoparticle-Based Herbal Drug Delivery Systems for Colon Targeting Therapy

Abstract: Herbal medications hold a dominant position in the pharmaceutical sector due to their well-established therapeutic effects and extremely low negative effects. Besides, herbal remedies are easily available and highly economical. However, to circumvent the issue of poor bioavailability, the combinatorial strategy of incorporating herbal medicines and nano-technology is useful. The phytoconstituents molded in novel nanocarriers such as polymeric nanoparticles, polymeric micelles, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, gold nanoparticles, etc., have been extensively investigated as they are the most promising approach for colon-targeting drug delivery systems. Although plant-based medicines have been developed for decades, there is enormous research interest in the development of an effective plant-derived delivery system for the incorporation of phytocon-stituents into various nanomaterials to overcome potential challenges related to solubility, bioavailability, and stability issues. The encapsulation of phytoconstituents in a novel nanocarrier is a promising approach to improving the bioavailability, stability, and therapeutic efficacy of herbal medicines. The herbal nanomedicines are used as a promising tool for tar-geted delivery to the colon, with potentially effective outcomes for the treatment of colonic diseases, viz., ulcerative colitis, diverticulitis, Crohn's disease, shigellosis, constipation, co-lonic polyps, colon cancer, etc. This article presents a comprehensive survey of recent find-ings and patents by innovators working exclusively on nanoparticles for the delivery of phy-tomedicines for colon targeting.

Corpi sofferenti d’amore. L’Ingénu di Voltaire tra intêret e sensibilité

In his conte philosophique L’Ingénu (1767), Voltaire engages in his philosophical battle through an original analysis of the love affair between the naïve protagonist Huron and Mademoiselle de Saint-Yves, a young Breton girl with a strict Catholic upbringing. The conflict between their desire to marry and the religious and political institutions is represented here by means of stylistic grafts belonging to the tradition of the genre of the sentimental novel, which in the middle of the 18th century was on the rise in France and the rest of Europe. Making the most recent discoveries in the medical-psychological field his own, Voltaire thus aims to establish the empathic bond on which the moral background of sentimental rhetoric was based through the representation of the psychological and physical suffering of the young protagonists. Distancing himself from the traditional concept of moral ‘virtue’ that was at the basis of the English sentimental novel, Voltaire thus instituted a reflection on amorous sentiment, now conceived not only as the main expression of the passion of individuals, but as a critical device to try to elaborate in an alternative way that reunion between private and public virtues that was at the basis of the Enlightenment mission.

Impact of Estrogen Therapy on BRCA1-Associated Breast Cancer Progression in Transgender Women

The combination of hormone treatment and genetic liabilities in transgender women leads to a complicated situation for breast cancer growth particularly linked to BRCA1 mutations. Gender-affirming treatment relies heavily on estrogen and causes intense cell growth and differentiation in breast tissue driven by estrogen receptor mechanisms. Mutations in BRCA1 lead to weak DNA repair processes which enhance an individual's vulnerability to cancerous changes. Rodestrogens enhance the functioning of proliferative pathways like PI3K/AKT and MAPK pathways in cells with dysfunctional BRCA1. This collaborative action elevates the threats posed by benign growths such as fibroadenomas leading to invasive breast cancer. By affecting the expression of vital regulatory proteins linked to cell proliferation estrogen further compromises the genomic integrity in cells harboring BRCA1 mutations. The hormone environment influenced by exogenous estrogen therapy can shape the tumor microenvironment for better cancer progression and metastasis. Comprehending the relationship between estrogen signaling and pathways related to BRCA1 is important for identifying the enhanced risk of cancer in transgender women using hormone therapy. This detailed study aligns recent discoveries regarding genetic vulnerability and hormonal impacts with cell mechanisms to reveal a detailed insight into breast cancer progression in these individuals. The study emphasizes the necessity for custom-designed cancer screening methods and targeted treatments to help mitigate risks and support transgender care. Understanding these pathways greatly enriches our knowledge of hormone-induced carcinogenesis among those who carry certain genetic markers while also guiding the creation of personalized care for transgender women at enhanced risk of breast cancer.

Epigenetic Regulation in Insect-Microbe Interactions.

Insects have evolved diverse interactions with a variety of microbes, such as pathogenic fungi, bacteria, and viruses. The immune responses of insect hosts, along with the dynamic infection process of microbes in response to the changing host environment and defenses, require rapid and fine-tuned regulation of gene expression programs. Epigenetic mechanisms, including DNA methylation, histone modifications, and noncoding RNA regulation, play important roles in regulating the expression of genes involved in insect immunity and microbial pathogenicity. This review highlights recent discoveries and insights into epigenetic regulatory mechanisms that modulate insect-microbe interactions. A deeper understanding of these regulatory mechanisms underlying insect-microbe interactions holds promise for the development of novel strategies for biological control of insect pests and mitigation of vector-borne diseases.

8627 Viral Hormones: The Role Of Viral Insulin/IGF-1 Like Peptides In Host-Pathogen Interactions

Abstract Disclosure: A. Chuard: None. Viruses, encode proteins that are similar to host proteins to manipulate the host. Until our recent discovery of viral hormones, examples of viral mimicry were limited to immunomodulatory proteins and growth factors. We recently showed that six viruses in Iridoviridae family encode genes mimicking human insulin and IGF-1. We previously chemically synthesizing these viral insulin/IGF-1 like peptides (VILPs) and showed that VILPs can bind to human insulin and IGF-1 receptor and further stimulate post-receptor signaling. VILPs also stimulate glucose uptake and proliferation in mammalian cells and lower the blood glucose in mice. Originally, VILP-carrying viruses were isolated from fish; however, the role of VILPs in viral pathogenesis is not studied in depth. Here, we examined the effects of Grouper Iridovirus (GIV, one of the VILP carrying viruses) infection and GIV-VILP on host insulin/IGF signaling system using fish cells.To this end, we chemically synthesized GIV-VILP in its single chain (sc, IGF-1 like) and double chain (dc, insulin-like) forms. Stimulation of grouper kidney (GK) and AB9 zebrafish cells with these peptides, insulin and IGF-1, showed that IGF-1 was the most potent ligand in these cells indicating an abundance of IGF-1 receptor (IGF1R). Further, both forms of the VILPs were as potent as insulin in its activity on receptor phosphorylation and post-receptor signaling. Examining the viral kinetics, we also showed that GIV32 gene (encoding GIV VILP) is an early viral gene in both cell types. Virion analysis through mass spectrometry indicated that VILPs are not viral structural proteins. On the other hand, analysis of the supernatant from infected cells indicated that VILPs are secreted peptides during the viral cycle. Our results with supernatant transfer experiments from infected cells to uninfected cells support the same conclusion that VILPs are secreted. The secreted VILPs initiate autophosphorylation of IGF1R and/or insulin receptor (IR), consequently triggering downstream cellular signaling and metabolism. Through the use of specific inhibitors for each receptor, we illustrated that IR signaling is crucial for GIV viral replication. Surprisingly, inhibition of IGF1R increased viral replication and we are currently examining potential inhibitory effects of GIV VILP. Furthermore, VILPs appear to exert a biased effect on the AKT pathway compared to the Erk pathway. Furthermore, the inhibition of the AKT pathway significantly reduces GIV viral replication. In summary, our findings reveal that GIV-VILP is actively produced during infection and contributes to the viral replication. To our knowledge, VILPs are the first hormone-mimics characterized in viral replication. Elucidating the role of VILPs in host-pathogen interactions, we propose a novel viral pathogenesis mechanism where viruses mimic host hormones to manipulate the host's endocrine system. Presentation: 6/3/2024

Characterizing the Metabolism of Tire Rubber-Derived p-Phenylenediamine Quinones to Identify Potential Exposure Biomarkers in Humans.

There is growing evidence of the frequent detection of tire rubber-derived contaminants p-phenylenediamine-derived quinones (PPD-Qs) (e.g., highly toxic N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q)) in the environment and biota and the adverse impact on organisms. Hence, a better understanding of their biotransformation/metabolism in humans is essential. However, relevant data are lacking owing to recent discoveries. Herein, the biotransformation patterns of 6PPD-Q and other five commonly detected PPD-Qs were characterized via combined in vitro assay and maternal cord blood screening monitoring. Rapid metabolism was found for each PPD-Q incubated with human liver S9 fraction and microsomes, resulting in the formation of abundant phase I and phase II metabolites. The subsequent screening for potential PPD-Q metabolites in blood samples showed the presence of suspect metabolites. Three detected metabolites were confirmed by matching the mass spectra and retention times of in vitro metabolites. N-Dealkylated, carboxy, carbonyl, and reductive metabolites and glucose, cysteine, and methionine conjugates were observed for the first time. The semiquantitative concentrations of metabolites were higher than those of the parent PPD-Qs, and several metabolites such as carboxy products were proposed as candidate biomarkers of PPD-Q exposure to humans. 6PPD-Q and N,N'-diphenyl-p-phenylenediamine quinone were detected in maternal and/or cord whole blood samples for the first time. This study holds great importance in elucidating the potential risks and health effects of PPD-Qs.

Reading m6A marks in mRNA: A potent mechanism of gene regulation in plants.

Modifications to RNA have recently been recognized as a pivotal regulator of gene expression in living organisms. More than 170 chemical modifications have been identified in RNAs, with N6-methyladenosine (m6A) being the most abundant modification in eukaryotic mRNAs. The addition and removal of m6A marks are catalyzed by methyltransferases (referred to as "writers") and demethylases (referred to as "erasers"), respectively. In addition, the m6A marks in mRNAs are recognized and interpreted by m6A-binding proteins (referred to as "readers"), which regulate the fate of mRNAs, including stability, splicing, transport, and translation. Therefore, exploring the mechanism underlying the m6A reader-mediated modulation of RNA metabolism is essential for a much deeper understanding of the epigenetic role of RNA modification in plants. Recent discoveries have improved our understanding of the functions of m6A readers in plant growth and development, stress response, and disease resistance. This review highlights the latest developments in m6A reader research, emphasizing the diverse RNA-binding domains crucial for m6A reader function and the biological and cellular roles of m6A readers in the plant response to developmental and environmental signals. Moreover, we propose and discuss the potential future research directions and challenges in identifying novel m6A readers and elucidating the cellular and mechanistic role of m6A readers in plants.

Deciphering visceral instincts: a scientific quest to unravel food choices from molecules to mind.

The study of biological mechanisms, while crucial, cannot fully explain complex phenomena like the instinct to eat. The mind-body connection, as exemplified by the concept of "voodoo death," highlights the profound influence of belief and cultural context on physiology. Indigenous knowledge systems further emphasize the interconnectedness of humans with their environment. Recent discoveries in gut-brain communication reveal the intricate neural circuits that drive our visceral desires, but a holistic approach that integrates both physiological mechanisms and the subjective experience of life, informed by diverse cultural perspectives, will be essential to truly understand what it means to be alive.

B-001 Serum 25-hydroxyvitamin D and C-3 epimer concentrations throughout gestation in a bovine dairy herd

Abstract Background Serum 25-hydroxyvitamin D (25(OH)D) serves as an indicator of vitamin D status in most animal species. The recent identification of its C-3 epimer, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3) remains diagnostically confounding. The appearance of this epimer in blood serum has been reported for both pregnant women and infants; however, because of its recent discovery, its physiologic role, biochemical regulation, and overall biologic importance have yet to be fully elucidated. Given its prevalence in pregnant women, it was hypothesized that 3-epi-25(OH)D3 may serve as a novel predictive biomarker of pregnancy in animals. Methods In the current study, we validated an LC-MS/MS method to measure the mono-hydroxyvitamin D metabolites 25-hydroxyvitamin D2 (25(OH)D2), 25-hydroxyvitamin D3 (25(OH)D3), and 3-epi-25(OH)D3, in bovine serum. Serum was collected from dairy cows at six stages of pregnancy (n=60 (10 per group), pre-breeding heifers, 30-40 days pregnant, 70-90 days, 120-180 days, 210-260 days, and 30-45 days post-calving). The 25(OH)D metabolites were extracted from serum by supported liquid extraction (SLE) and the eluate was derivatized with 2-Nitrosopyridine. Derivatized samples were introduced to the LC-MS/MS, ionized by electrospray ionization in positive-ion mode, and detected and quantified by multiple-reaction monitoring. Results The LC-MS/MS method was linear in the concentration range of 0.25 ng/mL to 100 ng/mL with an r2 > 0.99 for each analyte. 3-epi-25(OH)D3 and total serum 25(OH)D concentrations were calculated for each stage of pregnancy. Pre-bred heifers had serum 25(OH)D concentrations ranging from 65 - 85 ng/mL with trends toward non-significant increases with mean values approaching 100 ng/mL during pregnancy. Interestingly, 3-epi-25(OH)D3 remained near baseline (1.3 - 1.9 ng/mL) for the first 90 days and elevated 3- to 4-fold thereafter. Conclusions This study confirms that epimerization of 25(OH)D3 is a conserved biochemical process across species. While not predictive of pregnancy itself, the increase in circulating 3-epi-25(OH)D3 concentrations was consistent with mid- to late-gestational increases in estrogen concentration observed for dairy cattle. Future studies will explore the potential link between increases in gestational estrogen and epimerization.

Ferroptosis and myocardial ischemia-reperfusion: mechanistic insights and new therapeutic perspectives

Myocardial ischemia-reperfusion injury (MIRI) is a significant factor in the development of cardiac dysfunction following a myocardial infarction. Ferroptosis, a type of regulated cell death driven by iron and marked by lipid peroxidation, has garnered growing interest for its crucial involvement in the pathogenesis of MIRI.This review comprehensively examines the mechanisms of ferroptosis, focusing on its regulation through iron metabolism, lipid peroxidation, VDAC signaling, and antioxidant system dysregulation. We also compare ferroptosis with other forms of cell death to highlight its distinct characteristics. Furthermore, the involvement of ferroptosis in MIRI is examined with a focus on recent discoveries concerning ROS generation, mitochondrial impairment, autophagic processes, ER stress, and non-coding RNA regulation. Lastly, emerging therapeutic strategies that inhibit ferroptosis to mitigate MIRI are reviewed, providing new insights into potential clinical applications.