Primary Role Research Articles

Impact of Co and Cu co‐doping on the Structural, Electrical, Magnetic and Solar Light Driven Photo‐Catalytic Properties of NiFe2O4 Nano‐crystals for Crystal Violet Dye Removal

AbstractHerein, we have synthesised cobalt (Co) and copper (Cu) co‐doped Ni‐ferrite Ni1‐xCoxFe2‐yCuyO4 nanocrystals (NCs) via the facile micro‐emulsion method. The materials were analysed for various physio‐chemical characterizations to investigate the co‐doping (Co and Cu) effects on magnetic, structural, electrical, photo‐catalytic properties. The structural analysis via Fourier Transform Infrared spectroscopy (FTIR) and X‐rays diffraction (XRD) showed the successful fabrication of Co and Cu co‐doped materials with cubic spinel geometry having a single phase, the crystallite size was observed in 15 to 24 nm range. The electrical response measured using current‐voltage (I–V) analysis showed good electrical features, the electrical resistivity declined from 6.85×107 Ohm.cm for un‐doped materials to 0.04×107 Ohm.cm for co‐doped materials, which was accredited due to the synergistic effects of Co and Cu metal cations in co‐doped Ni‐based ferrite structures. Magnetic investigation using VSM analysis showed increased saturation magnetization (Ms 31.32 to 50.75 emu/g) and coercivity (218.76 to 406.82 Oe) because of the higher magnetic responses of Co2+ions in the co‐doped spinel ferrite NCs. BET surface‐area analysis showed good porosity for co‐doped materials with an increased surface area of 52 to 104 m2/g on co‐doping. The Tauc's plot described the decline of band‐gap energies value (Egs) (1.99 eV) in co‐doped (x=y=0.56) materials as compared to (2.16 eV) of the un‐doped NiFe2O4 materials, which is due to more electrical responses of Co and Cu co‐dopant cations that possess higher energy levels, which can stabilize the charge carrier‘s species. Furthermore, the photo‐degradation using solar light showed good removal of crystal violet (CV) dye, which was almost 94.14 % by co‐doped material; however, by un‐doped material, it was 38.044 %. The scavenger experiment shows that the (OH⋅) hydroxyl radicals and (e−/h+) species play a prime role in the degradation of CV dye. Recycling and recoverability tests for five cycles’ exhibited outstanding stability of the photocatalyst with only 1.7 % losses in activity. Overall, our results showed that co‐doped Ni1‐xCoxFe2‐yCuyO4 NCs materials exhibited enhancement in the magnetic, electrical, photo‐catalytic properties and a decline in band‐gap energy values as compared to un‐doped NiFe2O4, which might have potential use in magnetic and electrical devices as well as solar‐driven photo‐catalyst materials for the remediation of environmental pollution.

Antimicrobial resistance in the wild: Insights from epigenetics.

Spreading of bacterial and fungal strains that are resistant to antimicrobials poses a serious threat to the well-being of humans, animals, and plants. Antimicrobial resistance has been mainly investigated in clinical settings. However, throughout their evolutionary history microorganisms in the wild have encountered antimicrobial substances, forcing them to evolve strategies to combat antimicrobial action. It is well known that many of these strategies are based on genetic mechanisms, but these do not fully explain important aspects of the antimicrobial response such as the rapid development of resistance, reversible phenotypes, and hetero-resistance. Consequently, attention has turned toward epigenetic pathways that may offer additional insights into antimicrobial mechanisms. The aim of this review is to explore the epigenetic mechanisms that confer antimicrobial resistance, focusing on those that might be relevant for resistance in the wild. First, we examine the presence of antimicrobials in natural settings. Then we describe the documented epigenetic mechanisms in bacteria and fungi associated with antimicrobial resistance and discuss innovative epigenetic editing techniques to establish causality in this context. Finally, we discuss the relevance of these epigenetic mechanisms on the evolutionary dynamics of antimicrobial resistance in the wild, emphasizing the critical role of priming in the adaptation process. We underscore the necessity of incorporating non-genetic mechanisms into our understanding of antimicrobial resistance evolution. These mechanisms offer invaluable insights into the dynamics of antimicrobial adaptation within natural ecosystems.

A site-specific phosphorylation in FSTL1 determines its promigratory role in wound healing

Follistatin like-1 (FSTL-1) is a secreted glycoprotein of mesenchymal in origin. In human skin, FSTL1 is upregulated in the epidermal keratinocytes upon acute injury and is required for the migration of keratinocytes. Failure to upregulate FSTL1 leads to the lack of keratinocyte migration and the non-healing nature of diabetic foot ulcer (DFU). FSTL1 undergoes extensive post-translational modification (PTM) at specific residues. Glycosylation at N144, N175 and N180, are the only experimentally demonstrated PTM in FSTL1, wherein, N180 and N144 glycosylations have been found to be critical for its function in cardiac tissue regeneration and pre-adipocyte differentiation, respectively. However, it is not known if PTMs other than glycosylation occurs in FSTL1 and how it impacts its pro-migratory function. Using in-silico analysis of mass spectrometric datasets, we found a novel PTM, namely, Serine 165 (S165) phosphorylation in FSTL1. To address the role of S165 phosphorylation in its pro-migratory function, a phosphorylation defective mutant of FSTL1 (S165A) was constructed by converting serine 165 to alanine and over expressed in 293T cells. S165A mutation did not affect the secretion of FSTL1 in vitro. However, S165A abolished the pro-migratory effect of FSTL1 in cultured keratinocytes likely via its inability to facilitate ERK signaling pathway. Interestingly, bacterially expressed recombinant FSTL1, trans-dominantly inhibited wound closure in keratinocytes highlighting the prime role of FSTL1 phosphorylation for its pro-migratory function. Further, under high glucose conditions, which inhibited scratchwound migration of keratinocytes, we noticed a significant decrease in S165 phosphorylation. Taken together, our results reveal a hitherto unreported role of FSTL1 phosphorylation PTM with profound implications in wound healing.

Molecular priming with H2O2 and proline triggers antioxidant enzyme signals in maize seedlings during drought stress

BackgroundDrought and water stress impose major limitations to crops, including Maize, as they affect the plant biology at multiple levels. Drought activates the cellular signalling machinery to maintain the osmotic and ROS homeostasis for controlling plant response and adaptation to stress. Molecular priming of seeds plays a significant role in imparting stress tolerance by helping plants to remember the stress, which improves their response when they encounter stress again. MethodsIn this study, we examined the effect of priming maize seeds with H2O2 and proline, individually or in combination, on response to drought stress. We investigated the role of molecular priming on the physiological, biochemical and molecular response of maize seedlings during drought stress. ResultsWe observed that seed-priming played a significant role in mediating stress tolerance of seedlings under drought stress as indicated by changes in growth, biochemical properties, pigment and osmolyte accumulation, antioxidant enzyme activities, gas exchange parameters and gene expression. Seed-priming resulted in reduced expression of specific miRNAs to increase target transcripts associated with synthesis of osmolytes and maintenance of ROS homeostasis for reducing potential damage to the cellular components. ConclusionsSeed-priming induced changes in the growth, biochemical properties, pigment and osmolyte accumulation, antioxidant enzyme activities, gas exchange parameters and gene expression, though the response was dependent on the genotype, as well as concentration and combination of the priming agents.

Hybridization of concrete by the inclusions of kaolin, alumina and silica fume: Performance evaluation

Concrete is the prime source, which fulfils the applications for construction in various forms. The prime roles of concrete industries are reducing material usage, enrichment of compressive strength, and flexural strength of concrete usage. This research focuses on recycling kaolin (mining waste) and silica fume, a great potential material for replacing coarse aggregate gravel stone and fine aggregate sand in conventional concrete as a hybrid. The developed concrete contained 5% nano alumina (Al2O3), 10% of kaolin waste (KW), and 5, 10, and 15% of silica fume (SF), and its behavior like compressive strength, flexural strength, water absorption, and acid attack behavior is studied. The molecular structure of crystalline is analyzed via X-ray diffraction (XRD). The 15% SF blended with 5% alumina and 10% KW cured within 28 and 90 days recorded high compressive and flexural strength (44 ± 1.76 MPa and 4.3 ± 0.17 MPa). XRD pattern proved their alumina, SF, and KW and found that the concrete blended with 5% alumina, 10% KW, and 15 wt% SF(90 days cured concrete) showed low water absorption (3.1 ± 0.12%). The effect of sulfuric acid behavior on weight reduction was 0.78% compared to CC1 (concrete cube without Al2O3, SF, and KW).

EVALUATION OF INSECTICIDE APPLICATION FREQUENCY TO CONTROL SESAME LEAF WEBBER ANTIGASTRA CATALAUNALIS (DUPONCHEL) AND MIRID BUG CREONTIADUS DILUTES

Sesame (Sesamum indicum L.), a member of the Pedaliaceae family, is referred to as the queen of oilseeds. There are numerous barriers to its production and productivity, including a lack of economically feasible and technically adequate manufacturing technology, but insect pests particularly, sesame leaf webber (Antigastra catalaunalis) and Mirid Bug (Creontiadus dilutes) play a prime role in declining its potential yield. In this study, five treatments, viz. T1:2-WAE (weeks after emergence), T2:2,4-WAE, T3: 2,4,6 WAE, T4: 2,4,6,8 WEA, T5: weekly spray after emergence (positive control) and T6: control (zero application of spray) spray were applied, while T5=weekly spray started one week after emergence, prior to the onset of A. catalaunalis infestation on the sesame crop and was continuously applied until the maturity of the crop. A Hand knap sack sprayer was used for the Polytrin C 440EC (Profenophos 400 G/L + Cypermethrin G/L) @500ml/acre application. The results revealed that the incidence of A. catalaunalis and C. dilutes throughout the season during both years (2022-23) was significantly different (p < 0.001) among all treatments. High insecticide application frequency lowers the leaf, flower and capsule damage, which ultimately decreases seed loss and enhances the end product, so it was observed that T5: weekly spray after emergence (positive control) gave maximum control, followed by four-time spray application (T4: 2, 4, 6, 8WEA) while maximum infestation was observed in T6: control (zero application of spray), followed by T1:2-WAE. Positive control gave the best results. It is suggested that three-time spray application was found to be most suitable for the management of both devastating insects. Based on evaluation, it appears that adjusting the frequency of insecticide application can effectively control sesame leaf Webber and mirid bug populations. However, it’s important to balancer pest control with environmental concerns and resistance development.

The Impact of Social Media Usage in English Writing Among the High School Students in Selangor

Social media such as Twitter, Instagram, Facebook, and TikTok play a prime role in the 21st century as a communication medium. The development of the current technological world has led people to have a wide range of exposure to social media. In addition, regardless of age, almost everyone is exposed to and uses social media for entertainment, communication, and business purposes. However, it also proves that the younger generation is more addicted to the usage of social media. Despite social media playing a major role in effective communication in this current era, social media does impact high school students' English writing. Therefore, the aim of this study is to determine the frequency of social media usage and the impact of social media on high school students’ writing skills. Questionnaires were utilized as the major instrument to gather data for this study, and they were delivered to 30 secondary school students in Selangor. The data was analysed and summarised using frequencies and percentages, and the questionnaire was used to assist in the quantitative study design. Finally, data analysis has revealed that social media influences secondary school pupils' writing abilities.

Identification of small molecule inhibitors against Lin28/let-7 to suppress tumor progression and its alleviation role in LIN28-dependent glucose metabolism.

The reciprocal suppression of an RNA-binding protein LIN28 (human abnormal cell lineage 28) and miRNA Let-7 (Lethal 7) is considered to have a prime role in hepatocellular carcinoma (HCC). Though targeting this inhibition interaction is effective for therapeutics, it causes other unfavorable effects on glucose metabolism and increased insulin resistance. Hence, this study aims to identify small molecules targeting Lin28/let-7 interaction along with additional potency to improve insulin sensitivity. Of 22,14,996 small molecules screened by high throughput virtual screening, 6 molecules, namely 41354, 1558, 12437, 23837, 15710, and 8319 were able to block the LIN28 interaction with let-7 and increase the insulin sensitivity via interacting with PPARγ (peroxisome proliferator-activated receptors γ). MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) analysis is used to re-score the binding affinity of docked complexes. Upon further analysis, it is also seen that these molecules have superior ADME (Absorption, Distribution, Metabolism, and Excretion) properties and form stable complexes with the targets for a significant period in a biologically simulated environment (Molecular Dynamics simulation) for 100 ns. From our results, we hypothesize that these identified 6 small molecules can be potential candidates for HCC treatment and the glucose metabolic disorder caused by the HCC treatment.

PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.

Adaptive immunity relies on specialized effector functions elicited by lymphocytes, yet how antigen recognition activates appropriate effector responses through nonspecific signaling intermediates is unclear. Here we examined the role of chromatin priming in specifying the functional outputs of effector T cells and found that most of the cis-regulatory landscape active in effector T cells was poised early in development before the expression of the T cell antigen receptor. We identified two principal mechanisms underpinning this poised landscape: the recruitment of the nucleosome remodeler mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) by the transcription factors RUNX1 and PU.1 to establish chromatin accessibility at T effector loci; and a 'relay' whereby the transcription factor BCL11B succeeded PU.1 to maintain occupancy of the chromatin remodeling complex mSWI/SNF together with RUNX1, after PU.1 silencing during lineage commitment. These mechanisms define modes by which T cells acquire the potential to elicit specialized effector functions early in their ontogeny and underscore the importance of integrating extrinsic cues to the developmentally specified intrinsic program.

A clinical study to evaluate the efficacy of Aaditya Pak Guduchi Tail Shiroabhyanga in management of Khalitya (Baldness)

Introduction: In today’s corporate life, prime importance is given to our appearance, personality and beauty. Hair plays an important role in making body externally beautiful, healthy and good looking. Long hair makes a person mentally enthusiastic and healthy. Who are mostly suffering from this problem is the total population. Susceptibility of hair fall is more in male than in females. Methodology: Present study is carried out to know the traditional Ayurvedic treatment for Khalitya. For Khalitya Shiroabhyanga is one of the best choices of management for its prime role in maintaining hair growth and preventing Khalitya. Massage (Abhyanga) greatly improves the blood circulation, thus increasing the health of hair and also scalp. Result: The present study showed significant reduction in hair fall, dryness. Aaditya Pak Guduchi Tail was found effective in Khalitya along with significant effect on associated complaints. Conclusion: It also proves that Aaditya Pak Guduchi Tail is effective for use as Shiroabhyanga along with local application for scalp and hairs.

TSPYL1 as a Critical Regulator of TGFβ Signaling through Repression of TGFBR1 and TSPYL2.

Nucleosome assembly proteins (NAPs) have been identified as histone chaperons. Testis-Specific Protein, Y-Encoded-Like (TSPYL) is a newly arisen NAP family in mammals. TSPYL2 can be transcriptionally induced by DNA damage and TGFβ causing proliferation arrest. TSPYL1, another TSPYL family member, has been poorly characterized and is the only TSPYL family member known to be causal of a lethal recessive disease in humans. This study shows that TSPYL1 and TSPYL2 play an opposite role in TGFβ signaling. TSPYL1 partners with the transcription factor FOXA1 and histone methyltransferase EZH2, and at the same time represses TGFBR1 and epithelial-mesenchymal transition (EMT). Depletion of TSPYL1 increases TGFBR1 expression, upregulates TGFβ signaling, and elevates the protein stability of TSPYL2. Intriguingly, TSPYL2 forms part of the SMAD2/3/4 signal transduction complex upon stimulation by TGFβ to execute the transcriptional responses. Depletion of TSPYL2 rescues the EMT phenotype of TSPYL1 knockdown in A549 lung carcinoma cells. The data demonstrates the prime role of TSPYL2 in causing the dramatic defects in TSPYL1 deficiency. An intricate counter-balancing role of TSPYL1 and TSPYL2 in regulating TGFβ signaling is also unraveled.

Myokines: A central point in managing redox homeostasis and quality of life.

Redox homeostasis is a crucial phenomenon that is obligatory for maintaining the healthy status of cells. However, the loss of redox homeostasis may lead to numerous diseases that ultimately result in a compromised quality of life. Skeletal muscle is an endocrine organ that secretes hundreds of myokines. Myokines are peptides and cytokines produced and released by muscle fibers. Skeletal muscle secreted myokines act as a robust modulator for regulating cellular metabolism and redox homeostasis which play a prime role in managing and improving metabolic function in multiple organs. Further, the secretory myokines maintain redox homeostasis not only in muscles but also in other organs of the body via stabilizing oxidants and antioxidant levels. Myokines are also engaged in maintaining mitochondrial dynamics as mitochondria is a central point for the generation of reactive oxygen species (ROS). Ergo, myokines also act as a central player in communicating signals to other organs, including the pancreas, gut, liver, bone, adipose tissue, brain, and skin via their autocrine, paracrine, or endocrine effects. The present review provides a comprehensive overview of skeletal muscle-secreted myokines in managing redox homeostasis and quality of life. Additionally, probable strategies will be discussed that provide a solution for a better quality of life.

239 The Influence of Apolipoproteins E Gene Polymorphism on Cognitive Outcome in Patients with Moderate Degree Diffuse Brain Injuries

INTRODUCTION: APO-lipoproteins have a primary role in solubilizing and transporting lipids across cell membranes. APO-lipoprotein E isoform 4 (among APOE ε 1,2,3,4) is least efficient in clearing Aβ protein from the brain and is considered as a risk factor for Alzheimer disease. METHODS: After institutional ethics committee clearance, a prospective cohort study was done from 2017 to 2021 on adult patients who sustained moderate degree diffuse brain injury. APOE gene analysis were carried out on them. Patients who went on to subsequently develop focal lesions, those who died or were lost to follow up were excluded. Fifty consecutive patients who fulfilled the criteria, subsequently participate in a Mini Mental State Examination at the end of 1 month and 3 months were analysed. RESULTS: In our study, the allele frequencies for APOE gene ɛ2, ɛ3, ɛ4 were 36%, 53%, 11%, respectively. Patients were categorized into group A (who had at least one APOE ɛ4 allele) and group B (who did not have any APOE ɛ4 allele). In our study patients in group A had a prolonged hospitalisation and increased risk of convulsion than group B. The lack of improvement in MMSE scores (language and praxis subdomains) in group A as compared to group B after 3 months was statistically significant. The difference between the two groups in the rest of subdomains (attention, calculation, memory, orientation) and total MMSE scores at 3 months compared to that at discharge were insignificant. CONCLUSIONS: The presence of the APOE ɛ4 allele affects language and praxis during recovery. It increases the risk of post-traumatic seizures and increases the length of hospital stay but does not have a significant outcome on overall cognition after a course of 3 months.

Fast Enhancement of the Stratification in the Indian Ocean over the Past 20 Years

Abstract Indian Ocean (IO) stratification has important effects on the air–sea interaction, ocean dynamics, and ecology. It is, therefore, of significance to investigate the changes in IO stratification. In this study, we use ensemble empirical mode decomposition (EEMD) to extract the nonlinear long-term trend in the upper IO stratification quantified by potential energy anomalies. The results show that the strengthening of the stratification is spatially and temporally nonuniform. Specifically, the trend of stratification intensified gradually before 1996, but accelerated rapidly after 1996. Temperature and salinity changes play a crucial role in the fast enhancement of stratification and its regional differences. Temperature variations dominate the stratification trend in ∼90% of the IO area, while the contributions of salinity changes are mainly in the southeast Indian Ocean (SEIO). Vertically, the rapid enhancement of stratification is caused by the trend of temperature and salt in the upper 400 m. We further perform temperature budget analysis and find that the warming trend in the upper 400 m south of the IO is mainly modulated by vertical advection and meridional advection, while the warming in the north of the IO is mainly induced by air–sea heat fluxes. Salinity budget analysis shows that ocean advection has played a primary role in modulating SEIO salinity over the past 20 years.

Revitalising smallholder agriculture: the impact of technical training in rural Lebanon

AbstractThis paper provides new evidence about the impact of an agricultural development initiative focused on the cherry sector and implemented in rural areas of the Bekaa Valley (Lebanon). The initiative aims to enhance economic opportunities of smallholder farmers by strengthening technical skills, fostering sustainable productions and developing market linkages. Using original micro data from a sample of 118 smallholder cherry farmers, we explore, through a Difference-in-Differences approach, whether the development initiative, based on the provision of extension services and accompaniment through technical training, impacts on a broad set of alternative agricultural outcomes—namely, total cherry production, average market price, management competency and the adoption of improved agricultural practices. The results show that beneficiary small-scale farmers achieve better performances in three outcomes out of the four considered, with the adoption of improved and sustainable agricultural practices as the most remarkable result. Conversely, the management of the agricultural economic activity does not experience any statistically significant variation connected to the initiative implementation. The analysis of a limited source of treatment heterogeneity discloses the primary role of technical training, rather than other kinds of material support, to explain the main results.

Peptidome Profiling of Bubalus bubalis Urine and Assessment of Its Antimicrobial Activity against Mastitis-Causing Pathogens.

Urinary proteins have been studied quite exhaustively in the past, however, the small sized peptides have remained neglected for a long time in dairy cattle. These peptides are the products of systemic protein turnover, which are excreted out of the body and hence can serve as an important biomarker for various pathophysiologies. These peptides in other species of bovine have been reported to possess several bioactive properties. To investigate the urinary peptides in buffalo and simultaneously their bioactivities, we generated a peptidome profile from the urine of Murrah Buffaloes (n = 10). Urine samples were processed using <10 kDa MWCO filter and filtrate obtained was used for peptide extraction using Solid Phase Extraction (SPE). The nLC-MS/MS of the aqueous phase from ten animals resulted in the identification of 8165 peptides originating from 6041 parent proteins. We further analyzed these peptide sequences to identify bioactive peptides and classify them into anti-cancerous, anti-hypertensive, anti-microbial, and anti-inflammatory groups with a special emphasis on antimicrobial properties. With this in mind, we simultaneously conducted experiments to evaluate the antimicrobial properties of urinary aqueous extract on three pathogenic bacterial strains: S. aureus, E. coli, and S. agalactiae. The urinary peptides observed in the study are the result of the activity of possibly 76 proteases. The GO of these proteases showed the significant enrichment of the antibacterial peptide production. The total urinary peptide showed antimicrobial activity against the aforementioned pathogenic bacterial strains with no significant inhibitory effects against a buffalo mammary epithelial cell line. Just like our previous study in cows, the present study suggests the prime role of the antimicrobial peptides in the maintenance of the sterility of the urinary tract in buffalo by virtue of their amino acid composition.

Abstract 3401: Uncovering virus induced dysregulated processes in cancer and their impact on outcomes

Abstract The National Cancer Institute has designated several viruses such as EBV, HBV, HCV, HIV, HPV, and HTLV as agents that either cause cancer or increase the risk of developing cancer. However, extensive analyses of tumor genome and transcriptome datasets have identified numerous additional virus types, the functional implications of which remain largely unknown. Viral infection often dysregulates unique molecular processes within tumor cells and alters the composition of immune cells in the tumor microenvironment. For instance, HPV-positive tumors have been shown to exhibit a significantly elevated expression of the DNA editing enzyme APOBEC3B compared to HPV-negative tumors. Furthermore, HPV positive tumors display and increased number of C-to-T mutations induced by this protein. The genome and transcriptome of tumor tissue biopsies contain a wealth of information about these virus-associated signatures. However, advanced signal processing approaches are needed to extract these viral signatures from complex tumor datasets, and elucidate their specific roles in cancer. Here, we developed a quantitative approach to investigate the link between viral infection and dysregulation of a seven-membered A3 enzyme family (A3A/B/C/D/F/G/H). The primary role of these enzymes is to restrict viral infections by inducing C-to-U mutations in viral genomes. However, at least three members of this enzyme family (A3A/B/H) can also induce mutations in cellular DNA, and drive tumor formation and evolution. We used NMF (Nonnegative Matrix Factorization) to deconvolute the expression profiles of A3 enzymes in &amp;gt;10,000 bulk RNAseq datasets from diverse TCGA tumors. This analysis revealed the expression profiles of A3 enzymes within tumor and tumor microenvironment cells including various immune cells. Next, we conducted an association analysis to identify the link between the presence of viral infection and the proportion of each of these tumor and tumor microenvironment expression profiles. As expected, our analyses revealed strong associations between tumor-specific A3 expression profiles and infections by oncolytic viruses such as HPV. Notably, and somewhat unexpectedly, our analyses also revealed associations with viruses about which little is known in the field of cancer. For example, in certain tumors, we identified a robust association between bacteriophages and a tumor-specific A3 expression profile characterized by A3B upregulation. Taken together, our analyses provide evidence for the link between A3 dysregulation and infection by viruses including bacteriophages. Citation Format: Mohadeseh Soleimanpour moghadam, Azad Khosh, Diako Ebrahimi. Uncovering virus induced dysregulated processes in cancer and their impact on outcomes [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 3401.

Abstract 416: Development of substituted oxindole derivatives as a Ku-targeted DNA-PK inhibitors for cancer therapy

Abstract DNA double strand breaks (DSBs) are the most cytotoxic type of DNA damage. DSB repair pathway deficiency, often observed in cancer cells, results in translocations and genetic mutations that contribute to genomic instability. The generation of DNA DSBs is the primary mechanism of numerous chemo- and radio-therapeutic strategies used to treat various cancers. Modulating DSB repair pathways can have a profound impact on the clinical efficacy of DNA damaging therapies. DNA-dependent protein kinase (DNA-PK), which is composed of a DNA-PK catalytic subunit (DNA-PKcs) and Ku80-Ku70 heterodimer, acts as the molecular sensor for DSB and plays a prime role in DSB repair through non-homologous end joining (NHEJ). DNA-PK inhibitors become an attractive therapeutic target for cancer in combination with DSB-inducing radiotherapy and chemotherapy. There are at least 6-7 DNA-PK inhibitors in the preclinical and clinical stages which exhibit potential as treatment for various cancers. However, we have taken a unique and innovative approach to inhibiting DNA-PK via blocking the Ku70/80 heterodimer interaction with DNA, an essential step in DNA-PK activation and phosphorylation activity. Exploiting this unique mechanism of kinase activation, we have expanded our structure-activity relationships of pyrrolone derivatives. Modified synthetic schemes have been developed to allow a series of modifications to the X80 core structure. We have prepared furan, thiophene and pyrrole derivatives that enabled the identification of pharmacophores that impact in vitro potency and cellular off-target toxicity. Towards addressing cellular uptake and bioavailability, we identified substituted oxindole derivatives as potent Ku and DNA-PK inhibitors. These oxindole derivatives exhibited a better cellular uptake while retaining potent Ku inhibitory activity. Our data demonstrate that the cellular effects observed are a function of Ku inhibition and that this novel class of DNA-PK inhibitors can be further developed as anti-cancer therapeutics that can be used as an adjuvant to, or concomitant with radiotherapy and other cancer therapies that induce DNA damage. Citation Format: Dineshsinha Chauhan, Pamela L. Mendoza-Munoz, Narva Deshwar Kushwaha, Hariprasad Aruri, John J. Turchi, Navnath S. Gavande. Development of substituted oxindole derivatives as a Ku-targeted DNA-PK inhibitors for cancer therapy [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 416.

Integrative omics studies revealed synergistic link between sucrose metabolic isogenes and carbohydrates in poplar roots infected by Fusarium wilt.

Advances in carbohydrate metabolism prompted its essential role in defense priming and sweet immunity during plant-pathogen interactions. Nevertheless, upstream responding enzymes in the sucrose metabolic pathway and associated carbohydrate derivatives underlying fungal pathogen challenges remain to be deciphered in Populus, a model tree species. In silico deduction of genomic features, including phylogenies, exon/intron distributions, cis-regulatory elements, and chromosomal localization, identified 59 enzyme genes (11 families) in the Populus genome. Spatiotemporal expression of the transcriptome and the quantitative real-time PCR revealed a minuscule number of isogenes that were predominantly expressed in roots. Upon the pathogenic Fusarium solani (Fs) exposure, dynamic changes in the transcriptomics atlas and experimental evaluation verified Susy (PtSusy2 and 3), CWI (PtCWI3), VI (PtVI2), HK (PtHK6), FK (PtFK6), and UGPase (PtUGP2) families, displaying promotions in their expressions at 48 and 72h of post-inoculation (hpi). Using the gas chromatography-mass spectrometry (GC-MS)-based non-targeted metabolomics combined with a high-performance ion chromatography system (HPICS), approximately 307 metabolites (13 categories) were annotated that led to the quantification of 46 carbohydrates, showing marked changes between three compared groups. By contrast, some sugars (e.g., sorbitol, L-arabitol, trehalose, and galacturonic acid) exhibited a higher accumulation at 72 hpi than 0 hpi, while levels of α-lactose and glucose decreased, facilitating them as potential signaling molecules. The systematic overview of multi-omics approaches to dissect the effects of Fs infection provides theoretical cues for understanding defense immunity depending on fine-tuned Suc metabolic gene clusters and synergistically linked carbohydrate pools in trees.

Be(com)ing an Educational Researcher in the Global South (and Beyond): A Focus on the Research-Practice Relationship

Educational researchers are increasingly expected to focus on their research productivity as per their professional performance. Such a trend may have influenced their professional identities and activities, especially in the Global South, where researchers have not been immersed in the new research culture and where their assumed primary role may be to increase teaching efficacy instead. The pervasive focus on research productivity is detrimental to the equitable research-practice relationship whereby two groups of professionals—practitioners and researchers—collaboratively work to achieve the common goal of student learning. This teacher-researcher epistemological clash may exist within individual researchers when they have abundant teaching experience prior to becoming educational researchers. Through the lens of activity theory, we report on a case study of educational researchers’ lived experiences and struggles of navigating teacher-researcher identities in Chile, entailing their boundary-crossing of teacher-researcher identities, internal and external identity conflicts, and beliefs and actions related to the ideal research-practice relationship. In conclusion, we call for changes at the institutional level to promote an equitable and manageable research-practice relationship as well as at the individual level to reflect the ultimate purpose of educational research.