Resistance Strategies Research Articles

Glottopolitics of Prophecy

Abstract This article examines the secular use of prophecy and its appearances in Spain during the 2020 pandemic. It argues that prophecy functions as a cultural and political gesture with prescriptive potential over the future. As a glottopolitical tool (i.e., one that imbricates language and politics), it is contested between elites and subalterns articulating class warfare. Here, prophecy from above is analyzed through the concept of the “new normal,” which allowed Spanish politicians to predefine immediate future and safeguard the integrity of the capitalist system. As an example of prophecy from below, the article analyzes Lengua o muerte, a poetic text by Dani Zelko and the Movimiento por la lengua, which denounces the death of Mohammed Hossein during the pandemic as a case of linguistic discrimination. The author concludes that the discursive undertaking deployed in the book involves prophecy as a strategy of resistance against dispossession and projects a future of inclusion and emancipation.

A new perspective on antiangiogenic antibody drug resistance: Biomarkers, mechanisms, and strategies in malignancies.

Drug resistance of malignant tumor leads to disease progression be the bottleneck in clinical treatment. Antiangiogenic therapy, which aims to "starve" the tumor by inhibiting angiogenesis, is one of the key strategies in clinical oncology treatments. Recently, dozens of investigational antibody drugs and biosimilars targeting angiogenesis have obtained regulatory approval for the treatment of various malignancies. Moreover, a new generation of bispecific antibodies based on the principle of antiangiogenesis are being advanced for clinical trial to overcome antiangiogenic resistance in tumor treatment or enhance the efficacy of monotherapy. Tumors often develop resistance to antiangiogenesis therapy, presenting as refractory and sometimes even resistant to new therapies, for which there are currently no effective management strategies. Thus, a detailed understanding of the mechanisms mediating resistance to antiangiogenesis antibodies is crucial for improving drug effectiveness and achieving a durable response to antiangiogenic therapy. In this review, we provide a novel perspective on the tumor microenvironment, including antibody structure, tumor stroma, and changes within tumor cells, to analyze the multifactorial reasons underlying resistance to antiangiogenesis antibodies. The review also enumerates biomarkers that indicate resistance and potential strategies for monitoring resistance. Furthermore, based on recent clinical and preclinical studies, we summarize potential strategies and translational clinical trials aimed at overcoming resistance to antiangiogenesis antibodies. This review provides a valuable reference for researchers and clinical practitioners involved in the development of new drugs or therapeutic strategies to overcome antiangiogenesis antibodies resistance.

Evidence for a constitutive cost of host resistance on body fat growth in ewe lambs from lines selected for resistance or susceptibility to experimental infections with Haemonchus contortus

Although benefits of selection for host resistance to gastro-intestinal nematodes have long been recognized, its costs on production traits remain unclear. A main difficulty when studying those costs is to disentangle genetic effects due to selection from plastic responses induced by infection. Putative costs of host resistance have been extensively investigated in growing sheep. However, while most of those studies have relied on live weight to assess body growth, more comprehensive assessments accounting for body composition are advocated to detect trade-offs. In this study we used 90 female lambs from lines divergently selected on resistance to Haemonchus contortus that we experimentally infected (n = 60) or not (n = 30) under controlled conditions. As those conditions were defined to enable uninfected lambs to fully express their growth potential, we sought to precisely identify the effects of selection for host resistance on health traits and on growth traits. We assessed muscular and fat growth based on repeated measurements with dorsal ultrasonography for all lambs on farm, and with whole-body computed tomography (CT) scans for a subgroup of 18 infected lambs. Lambs achieved a high growth rate, including infected ones despite their high worm burden (confirmed at necropsy in the subgroup). As expected, lambs from the resistant (R) line were less infected than those from the susceptible (S) line. However, the clear pathogenic effects observed on muscular growth and voluntary feed intake were similar between lines. In contrast, a line difference in body fat was supported both by dorsal and volumetric CT measurements. Specifically, lower fat in the R line compared with the S line was observed equally in infected and uninfected groups, thus providing evidence for a constitutive cost of host resistance. Although this cost is not necessarily disadvantageous in nutrient-rich environments exposing animals to excess fat deposition, its consequences in nutrient-scarce environments may be important to promote sustainable breeding strategies for host resistance.

28P Targeting YAP1 as a biomarker of resistance and therapeutic strategy in melanoma immunotherapy

28P Targeting YAP1 as a biomarker of resistance and therapeutic strategy in melanoma immunotherapy

A Family Affair: Black Family Networks and the 1822 Vesey Conspiracy

Abstract: In 1822, white authorities in Charleston, South Carolina, discovered a major uprising among the city's free Black and enslaved population. After more than 100 people were arrested for their roles in the putative plot, sixty-seven people were convicted and either executed or banished from the country. While the episode, known as the Denmark Vesey conspiracy after the uprising's ringleader, is well-known to historians more generally, we know much less about how it affected the lived experiences of Black Charlestonians and how it influenced Black family networks. Although we know that women and sometimes children participated in slave insurrections like Vesey's conspiracy, we do not know how rebels used kinship ties to mobilize their resistive movements or what kind of precise impact violent resistance strategies had on Black communities in early America more broadly. Yet when analyzed through Black family networks, the conspiracy reveals how people used familial connections to spread insurrection and protect themselves from enslaver violence. Notwithstanding the use of these relationships to protect against chattel slavery, the conspiracy itself became another obstacle to their fight for freedom.

Long-term mold resistance strategy of laccase-catalyzed eugenol-modified bamboo and its antimicrobial mechanism derived from lignin

Bamboo, which has excellent physical properties and environmental credentials, is widely used in the construction industry and furniture manufacturing. Bamboo is, however, susceptible to attack by molds and bacteria; protection by natural phenolic antimicrobial agents would be a green and environmentally friendly solution to this problem. The application of such protection has, so far, been hampered by poor stability and ease of volatilization of the antimicrobial agent. Here, an innovative strategy that uses the catalytic action of the laccase to chemically attach a natural antimicrobial agent, eugenol (EU), to bamboo, is described. This modification endows bamboo with both long-lasting and extensive mold resistance and antibacterial activity. Laccase-catalyzed covalent bonding of EU to bamboo reduces the volatilization rate of the EU from 1.72 % to 0.29 %. The outstanding mold resistance and antimicrobial activity of bamboo treated using this modified process is retained during a 50-day mold resistance test, with mold growth inhibited by as much as 87.5 %. The treated bamboo is also able to inhibit the growth of both Gram-positive and Gram-negative bacteria. The antimicrobial mechanism results shown that the bamboo lignin is the primary reaction site during laccase-catalyzed EU modification of bamboo, and the long-term mold resistance derived from modified lignin. Furthermore, we analyzed bacterial morphology through SEM, and the results demonstrated that modified enzymatic hydrolysis lignin (EHL) significantly disrupts bacterial morphology, including membrane invagination and collapse. This study provides a new direction for the green development of mold- and bacteria-resistant bamboo, which has potential for use in a wide range of application.

Organizational change during economic downturns: Psychological drivers of employee resistance and management strategies

Organizational change during economic downturns: Psychological drivers of employee resistance and management strategies

Antioxidant Enzyme, Transcriptomic, and Metabolomic Changes in Lily (Lilium spp.) Leaves Induced by Aphis gossypii Glover.

Cotton aphids (Aphis gossypii Glover) cause harm by feeding on phloem sap and spreading plant viruses to lily. Understanding the mechanisms by which aphids infest lily plants is crucial for effective aphid management and control. In this study, we investigated the activity of antioxidants, integrated nontargeted metabolomes and transcriptomes of lilies infested by cotton aphids to explore the changes in lily leaves. Overall, the results indicated that the catalase (CAT) activity in the leaves of the lily plants was greater than that in the leaves of the control plants. A comprehensive identification of 604 substances was conducted in the leaves. Furthermore, the differentially abundant metabolite analysis revealed the enrichment of phenylalanine metabolism and α-linolenic acid metabolism. Moreover, 3574 differentially expressed genes (DEGs), whose expression tended to increase, were linked to glutathione metabolism and phenylpropanoid biosynthesis. In addition, the integrated analysis revealed that the defensive response of lily leaves to aphids is manifested through antioxidant reactions, phenylpropane and flavonoid biosynthesis, and α-linolenic acid metabolism. Finally, the key metabolites were CAT, glutathione, coumaric acid, and jasmonic acid, along with the key genes chalcone synthase (CHS), phenylalanine ammonia-lyase (PAL), and 12-oxo-phytodienoic acid reductase (OPR). Accordingly, the findings of this research elucidate the molecular and metabolic reactions of A. gossypii in lily plants, offering valuable insights for developing aphid resistance strategies in lily farming.

Molten CMAS resistance strategy for PS-PVD TBCs based on laser textured and Al-modified bionic structure

Plasma spray-physical vapor deposition (PS-PVD) is a promising third-generation thermal barrier coatings (TBCs) technique. Feather-like columnar TBCs with excellent strain tolerance and low thermal conductivity can be achieved using PS-PVD. However, molten CMAS (CaO–MgO–Al2O3–SiO2) can penetrate coatings and accelerate PS-PVD TBCs failure due to the feather-like columnar structure. Hence, a strategy is proposed to alleviate molten CMAS corrosion. The super-hydrophobicity structure is fabricated via laser texturing on the surface of PS-PVD TBCs to repel molten CMAS wetting and spreading. Then, a thin layer of the Al-film is deposited on the laser-textured surface. Next, the Al-modified layer is in situ synthesized after vacuum heat treatment, preventing the infiltration of molten CMAS into the TBCs and reducing the coating damage. The results show that the contact angle of laser textured and Al-modified PS-PVD TBCs (LT-Al) at room temperature increased from 12.3° to 168.8°. The wetting and spreading behavior of molten CMAS of as-sprayed (AS), laser textured (LT), and LT-Al coatings is observed in situ at 1230 °C for 1800 s. The LT-Al coatings exhibited excellent CMAS corrosion resistance, attributed to the laser-textured micro-nano structures and Al-modified layer protection. The findings may be an effective approach for solving the disadvantage of PS-PVD feather-like columnar structure TBCs.

Genetic determinants of increased sodium hypochlorite and ciprofloxacin susceptibility in Pseudomonas aeruginosa PA14 biofilms

Reactive chlorine species (RCS) like sodium hypochlorite (NaOCl) are potent oxidizing agents and widely used biocides in surface disinfection, water treatment, and biofilm elimination. Moreover, RCS are also produced by the human immune system to kill invading pathogens. However, bacteria have developed mechanisms to survive the damage caused by RCS. Using the comprehensive Pseudomonas aeruginosa PA14 transposon mutant library in a genetic screen, we identified a total of 28 P. aeruginosa PA14 mutants whose biofilms showed increased susceptibility to NaOCl in comparison to PA14 WT biofilms. Of these, ten PA14 mutants with a disrupted apaH, PA0793, acsA, PA1506, PA1547, PA3728, yajC, queA, PA3869, or PA14_32840 gene presented a 4-fold increase in NaOCl susceptibility compared to wild-type biofilms. While none of these mutants showed a defect in biofilm formation or attenuated susceptibility of biofilms toward the oxidant hydrogen peroxide (H2O2), all but PA14_32840 also exhibited a 2–4-fold increase in susceptibility toward the antibiotic ciprofloxacin. Further analyses revealed attenuated levels of intracellular ROS and catalase activity only for the apaH and PA1547 mutant, providing insights into the oxidative stress response in P. aeruginosa biofilms. The findings of this paper highlight the complexity of biofilm resistance and the intricate interplay between different mechanisms to survive oxidative stress. Understanding resistance strategies adopted by biofilms is crucial for developing more effective ways to fight resistant bacteria, ultimately contributing to better management of bacterial growth and resistance in clinical and environmental settings.

Potent and Protease Resistant Azapeptide Agonists of the GLP-1 and GIP Receptors.

The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play important physiological roles. Stabilized agonists of the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR) for the management of diabetes and obesity have generated widespread enthusiasm and have become blockbuster drugs. These therapeutics are refractory to the action of dipeptidyl peptidase-4 (DPP4), that catalyzes rapid removal of the two N-terminal residues of the native peptides, in turn severely diminishing their activity profiles. Here we report that a single atom change from carbon to nitrogen in the backbone of the entire peptide make them refractory to DPP4 action while still retaining full potency and efficacy at their respective receptors. This was accomplished by use of aza-amino acids, that are bioisosteric replacements for a-amino acids that perturb the structural backbone and local side chain conformations. Molecular dynamics simulations reveal that aza-amino acid can populate the same conformational space that GLP-1 adopts when bound to the GLP-1R. The insertion of an aza-amino acid at the second position from the N-terminus in semaglutide and in a dual agonist of GLP-1R and GIPR further demonstrates its capability as a viable alternative to current DPP4 resistance strategies while offering additional structural variety.

Delivering suburban densification: Diverse resident groups and strategies of support and resistance

Delivering suburban densification: Diverse resident groups and strategies of support and resistance

TRIM47 inhibits cisplatin chemosensitivity and endoplasmic reticulum stress-induced apoptosis of ovarian cancer cells

Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT–PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress–inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.

A RACIO-LINGUISTIC PERSPECTIVE OF LANGUAGE DISCRIMINATORY INSTANCES IN SCOTLAND

Racism has evolved to include not only skin colour but also linguistic discrimination, specifically targeting the use of the English language. Hence, educators and scholars have started acknowledging the language encounters of immigrants in Western society. This study intends to broaden the understanding of language discrimination experienced by immigrants in Scotland by examining the concepts of 'Linguistic strategy of resistance', 'ethnic accent bullying', and 'linguistic stereotyping'. The study uses questionnaires to elicit responses from 40 respondents and adopts a quantitative analytical approach for its analysis. Findings reveal that a significant proportion of migrants have encountered linguistic racism in many forms, including both explicit and implicit instances and in both formal and informal contexts. Some individuals can devise strategies to fight being abused or discriminated against linguistically, while others admit to allowing it to go unchallenged, resulting in psychological consequences. In conclusion, the study postulates that racism has indeed extended to the use of language, and despite the Western world's assertion of being post-racial, migrants in Scotland still face language-related discriminatory experiences daily.<p> </p><p><strong> Article visualizations:</strong></p><p><img src="/-counters-/soc/0770/a.php" alt="Hit counter" /></p>

SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. Statement of significanceSLC4A4 is a novel driver of enzalutamide resistance.

Mnemonic Strategies of Resistance: Environmental Analysts Resisting Bolsonaro

Mnemonic Strategies of Resistance: Environmental Analysts Resisting Bolsonaro

How Tea Plant Defends Against Blister Blight Disease: Facts Revealed and Unexplored Horizons.

Tea (Camellia sinensis [L.] O. Kuntze) is cultivated as a beverage crop. Despite being a hardy perennial, the tea plant is susceptible to various biotic stresses. Among them, the foliar disease blister blight (BB) is considered the most serious threat to the tea industry, particularly in Asia. BB caused by Exobasidium vexans (Basidiomycetes) was first reported from Northern India in 1868 and gradually established in other tea-growing countries. The fungus E. vexans attacks young harvestable shoots and causes 20 to 50% crop loss. Over the past 150 years, scientific research has delved into various aspects of BB disease, including pathogen biology, disease cycle, epidemiology, disease forecasting, crop loss assessment, and disease management strategies. In a recent shift in research focus, scientists have begun to investigate the resistance mechanisms of tea plants against BB and apply this knowledge to commercial tea cultivation. Although progress has been significant in understanding the fundamental aspects of BB resistance, the detailed molecular mechanisms driving this resistance remain under investigation. This paper focuses on the current understanding of defense mechanisms employed by tea plants against E. vexans and, conversely, how E. vexans overcomes these defenses. Furthermore, we discuss the application of plant resistance strategies in commercial tea cultivation. Lastly, we identify existing research gaps and propose future research directions in the field.

Empirically-Based Resistance Strategies: How Firms Resist Stakeholder Demands

Empirically-Based Resistance Strategies: How Firms Resist Stakeholder Demands

Identification of genes used by Escherichia coli to mitigate climatic stress conditions

IntroductionIncreasing temperature and elevated atmospheric carbon dioxide levels could impact the survival of stress-adapted bacteria. Method and resultsIn this study, RNA sequencing was performed to quantify Escherichia coli BL21 (DE3) gene expression in culture media under environmental temperature (27 °C and 42 °C) and carbon dioxide (0.2 % and 6 % v/v) conditions. Differential gene expression analysis between low temperature and different carbon dioxide conditions revealed up-regulated genes such as ldtC and bioA, optimising cell wall integrity and nutrient uptake. While, the downregulation of genes such as malK suggested a metabolic adaptation. Low temperature and high carbon dioxide levels enhanced bacterial tolerance to environmental stress. Under optimal temperatures, Escherichia coli adapts through various metabolic pathways while engaging in different processes at low temperatures and carbon dioxide levels, with temperature having a greater impact on gene expression than carbon dioxide levels. This study shows that complex metabolic activities are activated when both temperatures and carbon dioxide levels are combinsed, affecting antimicrobial resistance, nutrient acquisition, and adaptation strategies. ConclusionEach condition exhibited mechanisms to enhance cellular resilience and adaptation to stress, focusing on cellular integrity, optimising energy utilisation, and activating stress response pathways. Impact statementThe findings stress the importance of continued research to understand the implications of climate change on microbial transcriptomes comprehensively.

An overview of molecular mechanisms in cancer drug resistance and therapeutic strategies

Cancer resistance refers to the ability of cancer cells to evade the effects of treatments, such as chemotherapy and radiation, making it challenging to eliminate tumors. Cancer cells develop resistance through genetic modifications, alterations in cellular pathways, or microenvironmental adaptations that allow cancer cells to persist, proliferate, and even thrive despite the application of therapies designed to eradicate them. Despite efforts to create more potent target-based drugs, the flexibility of acquired resistance necessitates advanced options. Combination therapy and precision immunotherapy has revolutionized treatment but is limited by patient specificity and requires further development. New approaches like small molecules, peptides, and nanotherapeutics aim to overcome resistance by enhancing site-specific delivery and increasing drug concentration inside cancer cells. This review provides a comprehensive overview of the molecular mechanisms underlying cancer drug resistance, including genetic mutations, epigenetic alterations, efflux pump activity, and the influence of the tumor microenvironment. Additionally, the roles of microRNAs, long noncoding RNAs, and cellular processes such as autophagy and hypoxia in mediating resistance are examined. This review seeks to improve patient care and help to the development of more effective cancer medicines by explaining these complicated systems and investigating novel therapeutic alternatives.