Oncogenetics of Lung Cancer Induced by Environmental Carcinogens

The molecular landscape of non-tobacco-induced primary lung tumors displays specific oncogenetic features. The etiology of these tumors has been largely associated with exposure to well-established environmental lung carcinogens such as radon, arsenic, and asbestos. Environmental carcinogens can induce specific genetic and epigenetic alterations in lung tissue, leading to aberrant function of lung cancer oncogenes and tumor suppressor genes. These molecular events result in the disruption of key cellular mechanisms, such as protection against oxidative stress and DNA damage-repair, which promotes tumor development and progression. This chapter provides a comprehensive discussion of the specific carcinogenic mechanisms associated with exposure to radon, arsenic, and asbestos. It also summarizes the main protein-coding and non-coding genes affected by exposure to these environmental agents, and the underlying molecular mechanisms promoting their deregulation in lung cancer. Finally, the chapter examines the anticipated challenges in personalized intervention strategies in non-tobacco-induced lung cancer

Tumour Suppressor Genes with Oncogenic Roles in Lung Cancer

Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. High-throughput sequencing efforts have uncovered the molecular heterogeneity of this disease, unveiling several genetic and epigenetic disruptions driving its development. Unlike oncogenes, tumour suppressor genes negatively regulate cell cycle control and exhibit loss-of-function alterations in cancer. Although tumour suppressor genes are more frequently disrupted, oncogenes are more likely to be drug-targeted. Many genes are described as presenting both tumour suppressive and oncogenic functions in different tumour types or even within the natural history of the disease in a single tumour. In this chapter, we describe current knowledge of tumour suppressor genes in lung tissues, focusing on tumour suppressor/oncogene duality

Small Noncoding RNA Expression in Cancer

Despite an inability to encode proteins, small noncoding RNAs (sncRNAs) have critical functions in the regulation of gene expression. They have demonstrated roles in cancer development and progression and are frequently dysregulated. Here we review the biogenesis and mechanism of action, expression patterns, and detection methods of two types of sncRNAs frequently described in cancer: miRNAs and piRNAs. Both miRNAs and piRNAs have been observed to play both oncogenic and tumor-suppressive roles, with miRNAs acting to directly regulate the mRNA of key cancer-associated genes, while piRNAs play crucial roles in maintaining the integrity of the epigenetic landscape. Elucidating these important functions of sncRNAs in normal and cancer biology relies on numerous in silico workflows and tools to profile sncRNA expression. Thus, we also discuss the key detection methods for cancer-relevant sncRNAs, including the discovery of genes that have yet to be described

Profiling a decade of information systems frontiers’ research

This article analyses the first ten years of research published in the Information Systems Frontiers (ISF) from 1999 to 2008. The analysis of the published material includes examining variables such as most productive authors, citation analysis, universities associated with the most publications, geographic diversity, authors’ backgrounds and research methods. The keyword analysis suggests that ISF research has evolved from establishing concepts and domain of information systems (IS), technology and management to contemporary issues such as outsourcing, web services and security. The analysis presented in this paper has identified intellectually significant studies that have contributed to the development and accumulation of intellectual wealth of ISF. The analysis has also identified authors published in other journals whose work largely shaped and guided the researchers published in ISF. This research has implications for researchers, journal editors, and research institutions

Aberrant Expression of Pseudogene-Derived lncRNAs as an Alternative Mechanism of Cancer Gene Regulation in Lung Adenocarcinoma

Transcriptome sequencing has led to the widespread identification of long non-coding RNAs (lncRNAs). Subsequently, these genes have been shown to hold functional importance in human cellular biology, which can be exploited by tumors to drive the hallmarks of cancer. Due to the complex tertiary structure and unknown binding motifs of lncRNAs, there is a growing disparity between the number of lncRNAs identified and those that have been functionally characterized. As such, lncRNAs deregulated in cancer may represent critical components of cancer pathways that could serve as novel therapeutic intervention points. Pseudogenes are non-coding DNA sequences that are defunct relatives of their protein-coding parent genes but retain high sequence similarity. Interestingly, certain lncRNAs expressed from pseudogene loci have been shown to regulate the protein-coding parent genes of these pseudogenes in trans particularly because of this sequence complementarity. We hypothesize that this phenomenon occurs more broadly than previously realized, and that aberrant expression of lncRNAs overlapping pseudogene loci provides an alternative mechanism of cancer gene deregulation. Using RNA-sequencing data from two cohorts of lung adenocarcinoma, each paired with patient-matched non-malignant lung samples, we discovered 104 deregulated pseudogene-derived lncRNAs. Remarkably, many of these deregulated lncRNAs (i) were expressed from the loci of pseudogenes related to known cancer genes, (ii) had expression that significantly correlated with protein-coding parent gene expression, and (iii) had lncRNA protein-coding parent gene expression that was significantly associated with survival. Here, we uncover evidence to suggest the lncRNA-pseudogene-protein-coding gene axis as a prominent mechanism of cancer gene regulation in lung adenocarcinoma, and highlights the clinical utility of exploring the non-coding regions of the cancer transcriptome

The Top 100 questions for the sustainable intensification of agriculture in India’s rainfed drylands

India has the largest area of rainfed dryland agriculture globally, with a variety of distinct types of farming systems producing most of its coarse cereals, food legumes, minor millets, and large amounts of livestock. All these are vital for national and regional food and nutritional security. Yet, the rainfed drylands have been relatively neglected in mainstream agricultural and rural development policy. As a result, significant social-ecological challenges overlap in these landscapes: endemic poverty, malnutrition and land degradation. Sustainable intensification of dryland agriculture is essential for helping to address these challenges, particularly in the context of accelerating climate change. In this paper, we present 100 questions that point to the most important knowledge gaps and research priorities. If addressed, these would facilitate and inform sustainable intensification in Indian rainfed drylands, leading to improved agricultural production and enhanced ecosystem services. The horizon scanning method used to produce these questions brought together experts and practitioners involved in a broad range of disciplines and sectors. This exercise resulted in a consolidated set of questions covering the agricultural drylands, organized into 13 themes. Together, these represent a collective programme for new cross- and multi-disciplinary research on sustainable intensification in the Indian rainfed drylands

Hydrogeological system of erosional convergent margins and its influence on tectonics and interplate seismogenesis

[1] Fluid distribution in convergent margins is by most accounts closely related to tectonics. This association has been widely studied at accretionary prisms, but at half of the Earth's convergent margins, tectonic erosion grinds down overriding plates, and here fluid distribution and its relation to tectonics remain speculative. Here we present a new conceptual model for the hydrological system of erosional convergent margins. The model is based largely on new data and recently published observations from along the Middle America Trench offshore Nicaragua and Costa Rica, and it is consistent with observations from other erosional margins. The observations indicate that erosional margins possess previously unrecognized distinct hydrogeological systems: Most fluid contained in the sediment pores and liberated by early dehydration reactions drains from the plate boundary through a fractured upper plate to seep at the seafloor across the slope, rather than migrating along the décollement toward the deformation front as described for accretionary prisms. The observations indicate that the relative fluid abundance across the plate-boundary fault zone and fluid migration influence long-term tectonics and the transition from aseismic to seismogenic behavior. The segment of the plate boundary where fluid appears to be more abundant corresponds to the locus of long-term tectonic erosion, where tectonic thinning of the overriding plate causes subsidence and the formation of the continental slope. This correspondence between observations indicates that tectonic erosion is possibly linked to the migration of overpressured fluids into the overriding plate. The presence of overpressured fluids at the plate boundary is compatible with the highest flow rates estimated at slope seeps. The change from aseismic to seismogenic behavior along the plate boundary of the erosional margin begins where the amount of fluid at the fault declines with depth, indicating a control on interplate earthquakes. A previously described similar observation along accreting plate boundaries strongly indicates that fluid abundance exerts a first-order control on interplate seismogenesis at all types of subduction zones. We hypothesize that fluid depletion with depth increases grain-to-grain contact, increasing effective stress on the fault, and modifies fault zone architecture from a thick fault zone to a narrower zone of localized slip

The Evolution of Extracellular Fibrillins and Their Functional Domains

Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and non-elastic extracellular matrices, and are known to interact with several binding partners including tropoelastin and integrins. Here, we study the evolution of fibrillin proteins. Following sequence collection from 39 organisms representative of the major evolutionary groups, molecular evolutionary genetics and phylogeny inference software were used to generate a series of evolutionary trees using distance-based and maximum likelihood methods. The resulting trees support the concept of gene duplication as a means of generating the three vertebrate fibrillins. Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes. One of the genes significantly evolved to become the gene for present-day fibrillin-1, while the other underwent evolutionary changes, including a second duplication, to produce present-day fibrillin-2 and fibrillin-3. Detailed analysis of several sequences and domains within the fibrillins reveals distinct similarities and differences across various species. The RGD integrin-binding site in TB4 of all fibrillins is conserved in cephalochordates and vertebrates, while the integrin-binding site within cbEGF18 of fibrillin-3 is a recent evolutionary change. The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates. All collected sequences contain the first 9-cysteine hybrid domain, and the second 8-cysteine hybrid domain with exception of arthropods containing an atypical 10-cysteine hybrid domain 2. Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins. The four cysteines in the unique N-terminus and the two cysteines in the unique C-terminus are also highly conserved