Global Deregulation Research Articles

Analyzing India's National Civil Aviation Policy and Global Trends in Contemporary Civil Aviation Policies

The expansion of the Indian economy is expected to extend to remote regions, and while market-driven processes are ideal for regional air connectivity, there is recognition of the valuable role of public policy in this endeavor. The UDAN Scheme follows a market-oriented approach where operators assess demand, propose routes, and navigate variables like traffic rights, slot allocation, regulatory restrictions, and infrastructure limitations. Global airline industry deregulation has introduced healthy competition, enhancing efficiency and service quality, leading to increased passenger traffic. Studies have highlighted the constructive impact of improved air connectivity on the economic development of regions. Efficient airports are vital economic catalysts, but research suggests that some regional airports operate inefficiently, missing opportunities for profitability. Government subsidies and policies for enhancing regional and remote air connectivity are common practices worldwide, with schemes like EAS in the United State and PSO in Europe bridging the accessibility gap. Research is crucial to understand policy effects on air connectivity and identify factors that improve outcomes. Route dispersal guidelines, such as those in India, can create financial redistribution between route categories, affecting airlines' profitability and serving state capitals over remote regions. Policymakers must find effective ways to enhance air transport to underserved areas where market dynamics might not naturally establish viable transportation links. In summary, this study emphasizes the importance of government-supported policies like UDAN and the role of market-oriented approaches in promoting regional air connectivity. It underlines the need for research to assess policy impacts and identifies the challenges and opportunities in enhancing air connectivity to remote and underserved regions.

Epigenetic and transcriptional consequences in the endosperm of chemically induced transposon mobilization in Arabidopsis.

Genomic imprinting, an epigenetic phenomenon leading to parent-of-origin-specific gene expression, has independently evolved in the endosperm of flowering plants and the placenta of mammals-tissues crucial for nurturing embryos. While transposable elements (TEs) frequently colocalize with imprinted genes and are implicated in imprinting establishment, direct investigations of the impact of de novo TE transposition on genomic imprinting remain scarce. In this study, we explored the effects of chemically induced transposition of the Copia element ONSEN on genomic imprinting in Arabidopsis thaliana. Through the combination of chemical TE mobilization and doubled haploid induction, we generated a line with 40 new ONSEN copies. Our findings reveal a preferential targeting of maternally expressed genes (MEGs) for transposition, aligning with the colocalization of H2A.Z and H3K27me3 in MEGs-both previously identified as promoters of ONSEN insertions. Additionally, we demonstrate that chemically-induced DNA hypomethylation induces global transcriptional deregulation in the endosperm, leading to the breakdown of MEG imprinting. This study provides insights into the consequences of chemically induced TE remobilization in the endosperm, revealing that chemically-induced epigenome changes can have long-term consequences on imprinted gene expression.

Abstract 7074: Perturbed RNA N6-methyladenosine methylome in SETD2 mutant clear cell renal carcinoma

Abstract Clear cell renal carcinoma (ccRCC), which arises from the epithelial cells of the proximal tubule represents 70% of all renal cell carcinoma. Mutations that drive ccRCC in conjunction with near ubiquitous and early VHL loss include, PBRM1 (33 - 45%), BAP1 (15%) and SETD2 (13%). Loss of SETD2 leads to diminished occupancy of H3K36me3 in active gene bodies, which is progressively deregulated in primary RCC and metastasis, linking loss of H3K36me to tumor progression and metastasis. N6-Methyladenosine (m6A) is an important post-transcriptional regulator of RNA transcript stability and half-life. Preliminary findings have shown H3K36me3 (deposited by SETD2), targeting the core m6A methyltransferase machinery (METTL3, METTL14 and WTAP) to the mRNA by virtue of its interaction to METTL14 subunit. The goal of this study is to investigate if H3K36me3 depletion as observed in SETD2 mutant ccRCC, leads to a deregulated m6A methylome. We further investigate how deregulated methylome in key pathways leads to cancer initiation and progression in ccRCC. To accomplish our goals, we generated isogenic ccRCC cell lines with H3K36me3 depletion by knocking out SETD2. RNA-immunoprecipitation and sequencing for m6A (MeRIP) showed global deregulation of m6A methylome in SETD2KO isogenic ccRCC cell lines. We also show a number of pro-tumorigenic genes and pathways including cell invasion, inflammation and stemness being differentially methylated and expressed in SETD2KO ccRCC cell lines. Furthermore, we show SETD2KO cells being more sensitive to METTL3 inhibition suggesting the relevance of m6A hypermethylated transcripts in promoting pro-tumorigenic and growth promoting processes in SETD2KO ccRCC cell lines. Citation Format: Shafiq Shaikh, Ryan Wagner, Ryan Hlady, Keith D. Robertson. Perturbed RNA N6-methyladenosine methylome in SETD2 mutant clear cell renal carcinoma [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 7074.

Green finance: between commitment and illusion

PurposeAfter almost 10 years, people wonder if green finance has been able to attain its objectives in terms of controlling climate change. Persistent global warming and climate deregulation manifested by melting glaciers, droughts and floods, are all of these determinants that have called into question the efficiency of green finance.Design/methodology/approachGreen finance is a way to support climate action through investments. It has proven that this is a viable financial instrument and that it can be used by governments and private companies to plan for the future of our planet.FindingsBased on an analysis of articles published in top international journals from 2016 to 2022, about the relationship between green technology and financial services in China, this paper aims to present an overview of green finance, its importance for the planet, its objectives and its instruments.Research limitations/implicationsThis study’s contribution is to shed light on the aspects that may have limited its effectiveness, such as the absence of incentives, the absence of climate costs and above all the absence of finance green standards.Originality/valueThe results have shown that there is still a significant gap in green finance before inclusive green growth can be achieved. Inclusive green growth. All stakeholders need to increase the level of investment in green finance. The green investment financing gap is the result of inconsistencies in sustainability and policies. Therefore, governments must intervene to impose appropriate policies and regulations to compel the financial sector to engage in sustainable development. All of these factors make the concept of green finance just an illusion.

Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation.

Emerging evidence associates translation factors and regulators to tumorigenesis. However, our understanding of translational changes in cancer resistance is still limited. Here, we generated an enzalutamide-resistant prostate cancer (PCa) model, which recapitulated key features of clinical enzalutamide-resistant PCa. Using this model and poly(ribo)some profiling, we investigated global translation changes that occur during acquisition of PCa resistance. We found that enzalutamide-resistant cells exhibit an overall decrease in mRNA translation with a specific deregulation in the abundance of proteins involved in mitochondrial processes and in translational regulation. However, several mRNAs escape this translational downregulation and are nonetheless bound to heavy polysomes in enzalutamide-resistant cells suggesting active translation. Moreover, expressing these corresponding genes in enzalutamide-sensitive cells promotes resistance to enzalutamide treatment. We also found increased association of long non-coding RNAs (lncRNAs) with heavy polysomes in enzalutamide-resistant cells, suggesting that some lncRNAs are actively translated during enzalutamide resistance. Consistent with these findings, expressing the predicted coding sequences of known lncRNAs JPX, CRNDE and LINC00467 in enzalutamide-sensitive cells drove resistance to enzalutamide. Taken together, this suggests that aberrant translation of specific mRNAs and lncRNAs is a strong indicator of PCa enzalutamide resistance, which points towards novel therapeutic avenues that may target enzalutamide-resistant PCa.

Risk in “the Room:” Negotiating New Economic Paradigms in the Architecture of Lloyd’s of London Insurance Market

Today Richard Rogers + Partners’ Underwriting Room at Lloyd’s of London—known as “the Room”—is recognized as an icon of the High Tech movement, its modernity aestheticized through intersecting banks of escalators and a soaring twelve-story atrium. Yet on closer inspection, this interior represents a less satisfactory compromise. The product of years of protracted negotiations with a three hundred-year-old institution, the Room was conceived at a moment when the concept of risk, and the foundations of the insurance market, were transformed due to environmental crises, technological innovations and global financial deregulation. This paper contends that the changing nature of risk was mitigated through complex consultations over the design of the Room, simultaneously demanding new architectural solutions, whilst preserving the institution’s spatial and object-oriented rituals and mythologies. It concludes that the new Room, and the design process underpinning it, was a mode of institutional risk management in an age of uncertainty.

Фінансово-економічне стимулювання вторинного ресурсокористування в умовах децентралізації: сутність, принципи та регіональний вимір

The article substantiates the expediency of forming a modern system of financial and economic stimulation of the secondary resource use as a necessary prerequisite for activating the processes of utilization of secondary raw materials in the conditions of decentralization. The carried out studies have shown that the financial and economic stimulation of the secondary resource use is a logically ordered set of methods, instruments and levers of fiscal, budgetary, credit, price and reimbursement-penalty influence on the processes of involving the used industrial and household raw materials into economic circulation in order to use the resource value of its material and material substance. It is substantiated that the existing system of financial and economic stimuli for the secondary resource use, which operates at the national level, should receive its modification at the regional and local levels in order to make use of the most of the advantages and opportunities of decentralization in financial and investment support for the modernization of waste management infrastructure and the processes of disposal of the resource value of industrial and household waste. It is determined that the formation of a modern system of financial and economic stimulation of the secondary resource use should be based on a set of fundamental principles and the principles that imply compliance with the requirements of institutional transformations and conjuncture-cyclical fluctuations. It is substantiated that the fundamental principles of forming a system of financial and economic stimulation for the secondary resource use in the context of decentralization are the principles of environmental sustainability, economic efficiency and social responsibility, and the list of principles that provide for compliance with the requirements of institutional transformations and market-cycle fluctuations includes the principles of taking into account global benefits, decentralization and deregulation, adherence to the fiscal optimum, opportunity cost, complexity, prevention and elimination of negative externalities.

Internationalization journey of healthcare providers: The case of Turkish Acıbadem healthcare group

AbstractThe advances in technology and global deregulation have led to the progressive internationalization of professional services, notably, the healthcare industry. The present case study examines the remarkable internationalization journey of Acibadem Healthcare Group (AHG) by scrutinizing the dynamics and outcomes of the agile and innovative strategies which propel their achievements. The case of AHG shows that successful internationalization in the service industry, in general, and healthcare, in particular, is not solely in the domain of large, established companies from advanced economies, but those ventures with liabilities of origin, newness, and size can also succeed with smart strategies and resourceful leveraging of their competitive advantages. The study provides unique insights on strategic management for successful internationalization of the healthcare services within an emerging market context and suggests future research avenues in this fast‐growing field of inquiry.

The Effector Domain of the Influenza A Virus Nonstructural Protein NS1 Triggers Host Shutoff by Mediating Inhibition and Global Deregulation of Host Transcription When Associated with Specific Structures in the Nucleus.

ABSTRACTHost shutoff in influenza A virus (IAV) infection is a key process contributing to viral takeover of the cellular machinery and resulting in the downregulation of host gene expression. Analysis of nascently transcribed RNA in a cellular model that allows the functional induction of NS1 demonstrates that NS1 suppresses host transcription. NS1 inhibits the expression of genes driven by RNA polymerase II as well as RNA polymerase I-driven promoters, but not by the noneukaryotic T7 polymerase. Additionally, transcriptional termination is deregulated in cells infected with wild-type IAV. The NS1 effector domain alone is able to mediate both effects, whereas NS1 mutant GLEWN184-188RFKRY (184-188) is not. Overexpression of CPSF30 counteracts NS1-mediated inhibition of RNA polymerase II-driven reporter gene expression, but knockdown of CPSF30 expression does not attenuate gene expression. Although NS1 is associated with nuclear chromatin, superresolution microscopy demonstrates that NS1 does not colocalize with genomic DNA. Moreover, NS1 mutants and NS1 fusion proteins, unable to associate with nuclear chromatin and displaying an altered subcellular distribution are still able to attenuate reporter gene expression. However, tethering NS1 artificially to the cytoskeleton results in the loss of reporter gene inhibition. A NS1 deficient in both native nuclear localization signals (NLS) is able to inhibit gene expression as effective as wild-type NS1 when a synthetic NLS relocates it to specific structures of the nucleus. Colocalization experiments and reporter gene cotransfection experiments with a NS1 fusion guiding it to nuclear speckles suggest that the presence of NS1 in nuclear speckles seems to be essential for host shutoff.

Glucocorticoid-mediated induction of caveolin-1 disrupts cytoskeletal organization, inhibits cell migration and re-epithelialization of non-healing wounds

Although impaired keratinocyte migration is a recognized hallmark of chronic wounds, the molecular mechanisms underpinning impaired cell movement are poorly understood. Here, we demonstrate that both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) exhibit global deregulation of cytoskeletal organization in genomic comparison to normal skin and acute wounds. Interestingly, we found that DFUs and VLUs exhibited downregulation of ArhGAP35, which serves both as an inactivator of RhoA and as a glucocorticoid repressor. Since chronic wounds exhibit elevated levels of cortisol and caveolin-1 (Cav1), we posited that observed elevation of Cav1 expression may contribute to impaired actin-cytoskeletal signaling, manifesting in aberrant keratinocyte migration. We showed that Cav1 indeed antagonizes ArhGAP35, resulting in increased activation of RhoA and diminished activation of Cdc42, which can be rescued by Cav1 disruption. Furthermore, we demonstrate that both inducible keratinocyte specific Cav1 knockout mice, and MβCD treated diabetic mice, exhibit accelerated wound closure. Taken together, our findings provide a previously unreported mechanism by which Cav1-mediated cytoskeletal organization prevents wound closure in patients with chronic wounds.

Waterfront regeneration in Australia: Local responses to global trends in reimagining disused city docklands

AbstractThis article applies ideas about critical urban assemblages to understand the planning processes, politics, and delivery of waterfront regeneration from an Australian perspective, drawing on the Port Adelaide waterfront in South Australia as a case study. Waterfront regeneration is associated with global economic deregulation, market‐led development, changes to planning regulatory requirements, and “streamlined” governance arrangements. The global spread of waterfront regeneration is an outcome of such processes, with individual waterfronts being “remade” and reimagined to reflect priorities emphasised by those forging urban policies linked to inter‐urban competitiveness and neoliberal urbanism. Waterfront developments may be categorised as “models” of success or failure that limit deeper analysis that can advance theory and practice. How such projects reflect interactions across local and global scales rather than just being expressions of global forces is a question often ignored; so, too, are those considering how policy and politics mediate those relationships. Ideas, strategies, capital, people, policy, and politics are dynamic, provisional, and contested, and are produced and assembled in particular ways to suit specific spatiotemporal contexts. On that understanding, the aim of this article is to highlight how the Port Adelaide waterfront is undergoing assembly and reassembly to reflect socioeconomic priorities and metropolitan planning agendas.

The Role of Linker Histones in Carcinogenesis

Linker histones are DNA-binding architectural chromatin proteins involved in the formation of supranucleosomal levels of chromatin packaging. In mammals, 11 variants of these proteins are known, but the functional significance of this diversity is currently not fully defined. In addition to the main structural function, linker histones are involved in regulatory interactions, such as global gene deregulation during carcinogenesis. In turn, these changes in carcinogenesis can affect both linker histones through mutations of their encoding genes or changes in the expression of these genes, and the regulatory systems of the cell, causing a redistribution of linker histone variants in interphase chromatin, disrupting their posttranslational modifications or forming functionally active complexes with them. In some cases, changes in the metabolism of linker histones could be a possible cause of malignant transformation, as well as act as possible prognostic markers. Possible mechanisms of such changes in carcinogenesis are discussed, which also allow us to better understand the functions of linker histone variants and domains of these proteins in normal cells.

RTEL1 Regulates G4/R-Loops to Avert Replication-Transcription Collisions

SummaryRegulator of telomere length 1 (RTEL1) is an essential helicase that maintains telomere integrity and facilitates DNA replication. The source of replication stress in Rtel1-deficient cells remains unclear. Here, we report that loss of RTEL1 confers extensive transcriptional changes independent of its roles at telomeres. The majority of affected genes in Rtel1−/− cells possess G-quadruplex (G4)-DNA-forming sequences in their promoters and are similarly altered at a transcriptional level in wild-type cells treated with the G4-DNA stabilizer TMPyP4 (5,10,15,20-Tetrakis-(N-methyl-4-pyridyl)porphine). Failure to resolve G4-DNAs formed in the displaced strand of RNA-DNA hybrids in Rtel1−/− cells is suggested by increased R-loops and elevated transcription-replication collisions (TRCs). Moreover, removal of R-loops by RNaseH1 overexpression suppresses TRCs and alleviates the global replication defects observed in Rtel1−/− and Rtel1PIP_box knockin cells and in wild-type cells treated with TMPyP4. We propose that RTEL1 unwinds G4-DNA/R-loops to avert TRCs, which is important to prevent global deregulation in both transcription and DNA replication.

The global deregulation hypothesis

Abstract The growth of the American financial services remains a bit of a puzzle. The standard approach, the deregulation hypothesis, posits that the industry expanded in response to national deregulation. Yet, when viewed in a comparative context, US finance was deregulated significantly less than other national financial systems and yet grew significantly more than most. We propose the global deregulation hypothesis as a solution to this puzzle. The hypothesis posits that American finance grew in response to deregulation in Europe and the emerging market economies. The article develops two theoretical mechanisms that link global deregulation to US financialization. It reports statistical tests that support two central implications of the global deregulation hypothesis. First, global deregulation is positively associated with the growth of US financial services, while US deregulation is not. Second, global deregulation is not systematically related to the growth of financial services in other industrial democracies.

RTEL Resolves G4/R-Loops to Avert Replication-Transcription Collisions

RTEL1 is an essential helicase that maintains telomere integrity and facilitates DNA replication. The source of replication stress in Rtel1 deficient cells remains unclear. Here, we report that loss of RTEL1 confers extensive transcriptional changes independent of its roles at telomeres. The majority of affected genes in Rtel1-/- cells possess G4-DNA forming sequences in their promoters and are similarly altered at a transcriptional level in wild-type cells treated with the G4-DNA stabilizer TMPyP4. Failure to resolve G4-DNAs formed in the displaced strand of RNA-DNA hybrids in Rtel1-/- cells is suggested by increased R-loops and elevated transcription-replication collisions (TRCs). Moreover, removal of R-loops by RNaseH1 overexpression suppresses TRCs and alleviates the global replication defects observed in Rtel1-/-, Rtel1PIP_box knock-in cells and in wild type cells treated with TMPyP4. We propose that RTEL1 unwinds G4-DNA/R-loops to avert TRCs, which is important to prevent global deregulation in both transcription and DNA replication.

Abstract A39: Molecular characterization of ETMRs reveals role for R-loop mediated genomic instability and new treatment options

Abstract Introduction: Embryonal tumors with multilayered rosettes (ETMRs) are aggressive brain tumors that occur mainly in infants. Patients face a very poor prognosis with a median overall survival of ~12 months after diagnosis. The tumors harbor in ~90% of all cases amplification of a miRNA cluster on chromosome 19 (C19MC) that is thought to be the driver of the disease. However, current treatment options are lacking as (a) the mechanisms downstream of C19MC are poorly understood and (b) the drivers in cases lacking the C19MC aberration are unknown. To develop better treatment protocols for ETMR patients, more insight is needed in what is driving these tumors and how that can be targeted. Materials and Methods: To investigate the genomic and epigenomic landscape of ETMR in depth, we collected 193 ETMR samples and 23 matched relapses and performed DNA methylation profiling on all and DNA (whole genome, whole exome, and panel) sequencing and mRNA and miRNA transcriptome analysis on a subset of them. The BT183 ETMR cell line was used for drug treatments. Results: Among the 22 tumors without C19MC amplification, we identified 8 cases with truncating DICER1 germline mutations in one allele and somatic missense mutations in the RNASE III domain in the other allele. No DICER1 mutations were identified in C19MC amplified cases. In addition, structural variations (SVs) affecting C19MC were found in 3 other C19MC nonamplified cases and amplification of another miRNA cluster, miR-17-92, in 2 other cases. However, despite the presence of different genetic aberrations, based on DNA methylation and transcriptome profiling no molecular subgrouping was observed within our cohort. Whole-genome sequencing revealed an overall low recurrence and conservation of SNVs but strong conservation of SVs from primary tumors to relapses, especially surrounding C19MC. Moreover, many newly acquired SNVs in the relapses are associated to a new cisplatin treatment-related mutational signature. SVs detected in ETMRs significantly colocalized with R-loops, structures that form upon a collision of replication and transcription and are associated to increased levels of chromosomal instability, which is frequently observed in ETMRs. Using a DICER1 KO model, we found that global deregulation of miRNAs led to increased levels of R-loops and R-loop associated chromosomal instability. Finally, we show that a combination of topoisomerase and PARP inhibitors is highly synergistic and strongly increased the levels of both R-loops and DNA damage in ETMR cells and effectively killed the cells. Conclusions: Our results show that genomically instable ETMR cells are vulnerable to further increases in chromosomal instability, knowledge that may lead to new treatment strategies for ETMR patients and possibly other cancers with high levels of R-loops. Citation Format: Sander Lambo, Susanne Grübner, Tobias Rausch, Sebastian Waszak, Christin Schmidt, Sonja Krausert, Loreen Weichert, Aparna Gorthi, Carolina Romero, Annie Huang, Julia Schueler, Jan Korbel, Alexander Bishop, Stefan Pfister, Andrey Korshunov, Marcel Kool. Molecular characterization of ETMRs reveals role for R-loop mediated genomic instability and new treatment options [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A39.

Pharmacological inhibition of lysine-specific demethylase 1 (LSD1) induces global transcriptional deregulation and ultrastructural alterations that impair viability in Schistosoma mansoni.

Treatment and control of schistosomiasis still rely on only one effective drug, praziquantel (PZQ) and, due to mass treatment, the increasing risk of selecting for schistosome strains that are resistant to PZQ has alerted investigators to the urgent need to develop novel therapeutic strategies. The histone-modifying enzymes (HMEs) represent promising targets for the development of epigenetic drugs against Schistosoma mansoni. In the present study, we targeted the S. mansoni lysine-specific demethylase 1 (SmLSD1), a transcriptional corepressor, using a novel and selective synthetic inhibitor, MC3935, which was used to treat schistosomula and adult worms in vitro. By using cell viability assays and optical and electron microscopy, we showed that treatment with MC3935 affected parasite motility, egg-laying, tegument, and cellular organelle structures, culminating in the death of schistosomula and adult worms. In silico molecular modeling and docking analysis suggested that MC3935 binds to the catalytic pocket of SmLSD1. Western blot analysis revealed that MC3935 inhibited SmLSD1 demethylation activity of H3K4me1/2. Knockdown of SmLSD1 by RNAi recapitulated MC3935 phenotypes in adult worms. RNA-Seq analysis of MC3935-treated parasites revealed significant differences in gene expression related to critical biological processes. Collectively, our findings show that SmLSD1 is a promising drug target for the treatment of schistosomiasis and strongly support the further development and in vivo testing of selective schistosome LSD1 inhibitors.

Comparative analysis of metabolic and transcriptomic features of Nothobranchius furzeri.

Some species have a longer lifespan than others, but usually lifespan is correlated with typical body weight. Here, we study the lifetime evolution of the metabolic behaviour of Nothobranchius furzeri, a killifish with an extremely short lifespan with respect to other fishes, even when taking into account rescaling by body weight. Comparison of the gene expression patterns of N. furzeri with those of zebrafish Danio rerio and mouse (Mus musculus) shows that a broad set of metabolic genes and pathways are affected in N. furzeri during ageing in a way that is consistent with a global deregulation of chromatin. Computational analysis of the glycolysis pathway for the three species highlights a rapid increase in the metabolic activity during the lifetime of N. furzeri with respect to the other species. Our results highlight that the unusually short lifespan of N. furzeri is associated with peculiar patterns in the metabolic activities and in chromatin dynamics.

Differential expression of circulating serum miR-1249-3p, miR-3195, and miR-3692-3p in non-small cell lung cancer.

Global deregulation in miRNA expression is a hallmark of cancer cell. An estimated 2300 mature miRNAs are encoded by human genome; role of many of which in carcinogenesis and as cancer biomarkers remains unexplored. In this study, we investigated the utility of miR-3692-3p, miR-3195, and miR-1249-3p as biomarkers in non-small cell lung cancer (NSCLC). For this prospective study, 115 subjects, including 75 NSCLC patients and 40 controls, were recruited. The expression of miR-3692-3p, miR-3195, and miR-1249-3p was checked using qRT-PCR. The miRNA expression was correlated with survival outcome and therapeutic response. There were no significant differences in the mean age of NSCLC patients and controls (56.2 and 55.3years, respectively; p = 0.3242). Majority of NSCLC patients (67%) were smokers. We observed a significant upregulation of miR-3692-3p expression (p < 0.0001), while the expression of miR-3195 (p = 0.0017) and miR-1249-3p was significantly downregulated (p < 0.0001) in the serum of NSCLC patients as compared to controls. The expression of miR-1249-3p was significantly upregulated in lung adenocarcinoma versus lung squamous cell carcinoma (p = 0.0178). Interestingly, patients who responded to chemotherapy had higher expression of miR-1249-3p than non-responders (p = 0.0107). Moreover, patients with higher expression of miR-3195 had significantly longer overall survival (p = 0.0298). In multivariate analysis, miR-3195 emerged as independent prognostic factor for overall survival. We conclude that the miR-3195 may have prognostic significance, while miR-1249-3p may predict therapeutic response in NSCLC. Further studies are warranted to elucidate the role of these miRNAs in lung carcinogenesis and their utility as candidate cancer biomarkers.

The variety and limits of dairy policies in a context of global market deregulation

Since the 1980s, agricultural markets have been gradually deregulated. The milk sectors of the main dairy-exporting countries have not been shielded from these changes, which has led to a deeper global integration of dairy markets. However, a historical comparison of policies in the United States, New Zealand, the European Union, and Canada, from both a rural economy and regulationist perspective, reveals that a variety of institutional frameworks exist. For instance, Canada’s dairy sector continues to be highly regulated by public authorities, unlike in the case of New Zealand. Both countries, though, along with the United States, guarantee farmers a minimum share of the added value from processing, contrary to what is practiced in France. Market deregulation in the European Union has also brought about different national forms of competition. Based on the dairy sector, this analysis supports the idea of a great diversity of national forms of state and regulation, adapting to the global capitalist and neo-liberal regime. However, the latter generates major contradictions, disputing the sustainability of each of these forms of national regulation.