112 research outputs found

    Cigarette-Smoke-Induced Dysregulation of MicroRNA Expression and Its Role in Lung Carcinogenesis

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    Dysregulation of microRNAs (miRNAs), particularly their downregulation, has been widely shown to be associated with the development of lung cancer. Downregulation of miRNAs leads to the overactivation of their oncogene targets, while upregulation of some miRNAs leads to inhibition of important tumor suppressors. Research has implicated cigarette smoke in miRNA dysregulation, leading to carcinogenesis. Cigarette smoke may lead to genetic or epigenetic damage to miRNAs, many of which map to fragile sites and some of which contain single nucleotide polymorphisms. Cigarette smoke may also cause dysregulation by affecting regulatory mechanisms controlling miRNA expression. Researchers have shown a correlation between smoke-exposure-induced dysregulation of miRNAs and age. Furthermore, dysregulation seems to be associated with intensity and duration of smoke exposure and duration of cessation. Longer exposure at a threshold level is needed for irreversibility of changes in expression. Better understanding of miRNA dysregulation may allow for improved biomonitoring and treatment regimens for lung cancer

    THE EFFECT OF FINANCIAL AND CORPORATE GOVERNANCE FACTORS ON THE FORCED FINANCIAL RESTATEMENT LIKELIHOOD: EVIDENCE FROM MALAYSIA

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    Background and Purpose: Forced financial restatement (FFR) creates a major concern as it has an instantaneous and disastrous effect on a firm’s share price. Whilst studies focusing on FFR are limited, this study investigated the financial and corporate governance influences that affect the FFR likelihood within the emerging background of Malaysia. This study aims to provide new evidence and insights to Malaysian regulators in developing strategies to reinforce financial reporting quality.   Methodology: The influences of board independence, political connection, audit committee financial expertise, government-related institutional ownership, family ownership and control, corporate reporting quality, and financial distress on FFR occurrence were investigated. A multivariate logistic model was employed on 4,759 firm-year observations from 2002 until 2012. Findings: Findings revealed that aggressive accounting influences the FFR likelihood. Based on the results, the number of independent board directors, the presence of politically connected investors or management, working capital accruals management, real earnings management, and the financial health of the firm amplified the FFR occurrences.   Contributions: This study enriches the body of knowledge on FFR by investigating a wider range of financial and corporate governance factors as possible determinants of FFR.   Keywords: Forced financial restatement, opportunistic, accruals management, real earnings management, Malaysia.   Cite as: Slack, R., Othman, I. W., Stratling, R., Syed-Yusuf, S. N., & Wan Mohd Radzi, W. S. (2023). The effect of financial and corporate governance factors on the forced financial restatement likelihood:  Evidence from Malaysia. Journal of Nusantara Studies, 8(TI), 147-176. http://dx.doi.org/10.24200/jonus.vol8issTIpp147-17

    Chromosome-level assembly reveals extensive rearrangement in sakar falcon and budgerigar, but not ostrich, genomes

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    Background: The number of de novo genome sequence assemblies is increasing exponentially; however, relatively few contain one scaffold/contig per chromosome. Such assemblies are essential for studies of genotype-to-phenotype association, gross genomic evolution, and speciation. Inter-species differences can arise from chromosomal changes fixed during evolution, and we previously hypothesized that a higher fraction of elements under negative selection contributed to avian-specific phenotypes and avian genome organization stability. The objective of this study is to generate chromosome-level assemblies of three avian species (saker falcon, budgerigar, and ostrich) previously reported as karyotypically rearranged compared to most birds. We also test the hypothesis that the density of conserved non-coding elements is associated with the positions of evolutionary breakpoint regions. Results: We used reference-assisted chromosome assembly, PCR, and lab-based molecular approaches, to generate chromosome-level assemblies of the three species. We mapped inter- and intrachromosomal changes from the avian ancestor, finding no interchromosomal rearrangements in the ostrich genome, despite it being previously described as chromosomally rearranged. We found that the average density of conserved non-coding elements in evolutionary breakpoint regions is significantly reduced. Fission evolutionary breakpoint regions have the lowest conserved non-coding element density, and intrachromomosomal evolutionary breakpoint regions have the highest. Conclusions: The tools used here can generate inexpensive, efficient chromosome-level assemblies, with > 80% assigned to chromosomes, which is comparable to genomes assembled using high-density physical or genetic mapping. Moreover, conserved non-coding elements are important factors in defining where rearrangements, especially interchromosomal, are fixed during evolution without deleterious effects

    Pharmacological characterization of the αvβ6 integrin binding and internalization kinetics of the foot-and-mouth disease virus derived peptide A20FMDV2

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    A20FMDV2 is a peptide derived from the foot-and-mouth disease virus with a high affinity and selectivity for the alphav beta-6 (αvβ6) arginyl-glycinyl-aspartic acid (RGD)-binding integrin. It has been shown to be an informative tool ligand in pre-clinical imaging studies for selective labelling of the αvβ6 integrin in a number of disease models. In a radioligand- binding assay using a radiolabelled form of the peptide ([3H]A20FMDV2), its high affinity (KD:0.22nmol/l) and selectivity (at least 85-fold) for αvβ6 over the other members of the RGD integrin family was confirmed. [3H]A20FMDV2 αvβ6 binding could be fully reversed only in the presence of EDTA, whereas a partial reversal was observed in the presence of excess concentrations of an RGD-mimetic small molecule (SC-68448) or unlabelled A20FMDV2. Using flow cytometry on bronchial epithelial cells, the ligand-induced internalization of αvβ6 by A20FMDV2 and LAP1 was shown to be fast (t1/2:1.5and 3.1 min, respectively), concentration-dependent (EC50:values 1.1 and 3.6nmol/l, respectively) and was followed by a moderately slow return of integrin to the surface. The results of the radioligand-binding studies suggest that the binding of A20FMDV2 to the RGD-binding site on αvβ6 is required to maintain its engagement with the hypothesised A20FMDV2 synergy site on the integrin. In addition, there is evidence from flow cytometric studies that the RGD-ligand engagement of αvβ6 post-internalization plays a role in delaying recycling of the integrin to the cell surface. This mechanism may act as a homeostatic control of membrane αvβ6 following RGD ligand engagement

    User-centered development of a Virtual Research Environment to support collaborative research events

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    This paper discusses the user-centred development process within the Collaborative Research Events on the Web (CREW) project, funded under the JISC Virtual Research Environments (VRE) programme. After presenting the project, its aims and the functionality of the CREW VRE, we focus on the user engagement approach, grounded in the method of co-realisation. We describe the different research settings and requirements of our three embedded user groups and the respective activities conducted so far. Finally we elaborate on the main challenges of our user engagement approach and end with the project’s next steps

    A National Plan for Assisting States, Federal Agencies, and Tribes in Managing White-Nose Syndrome in Bats

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    White-nose syndrome (WNS) is a disease responsible for unprecedented mortality in hibernating bats in the northeastern U.S. This previously unrecognized disease has spread very rapidly since its discovery in January 2007, and poses a considerable threat to hibernating bats throughout North America. As WNS spreads, the challenges for understanding and managing the disease continue to increase. Given the escalating complexity of these challenges, a highly coordinated effort is required for State, Federal, and Tribal wildlife agencies, and private partners to respond effectively to WNS and conserve species of bats. The plan proposed herein details the elements that are critical to the investigation and management of WNS, identifies key action items to address stated goals, and outlines the role(s) of agencies and entities involved in this continental effort

    Characterization of a Bacillus anthracis spore coat-surface protein that influences coat-surface morphology

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    Bacterial spores are encased in a multilayered proteinaceous shell, called the coat. In many Bacillus spp., the coat protects against environmental assault and facilitates germination. In Bacillus anthracis , the spore is the etiological agent of anthrax, and the functions of the coat likely contribute to virulence. Here, we characterize a B. anthracis spore protein, called CotΒ, which is encoded only in the genomes of the Bacillus cereus group. We found that CotΒ is synthesized specifically during sporulation and is assembled onto the spore coat surface. Our analysis of a cotΒ null mutant in the Sterne strain reveals that CotΒ has a role in determining coat-surface morphology but does not detectably affect germination. In the fully virulent Ames strain, a cotΒ null mutation has no effect on virulence in a murine model of B. anthracis infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72138/1/j.1574-6968.2008.01380.x.pd

    Expanding the Diagnostic Use of PCR in Leptospirosis: Improved Method for DNA Extraction from Blood Cultures

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    Background: Leptospirosis is a neglected zoonosis of ubiquitous distribution. Symptoms are often non-specific and may range from flu-like symptoms to multi-organ failure. Diagnosis can only be made by specific diagnostic tests like serology and PCR. In non-endemic countries, leptospirosis is often not suspected before antibiotic treatment has been initiated and consequently, relevant samples for diagnostic PCR are difficult to obtain. Blood cultures are obtained from most hospitalized patients before antibiotic therapy and incubated for at least five days, thus providing an important source of blood for PCR diagnosis. However, blood cultures contain inhibitors of PCR that are not readily removed by most DNAextraction methods, primarily sodium polyanetholesulfonate (SPS). Methodology/Principal Findings: In this study, two improved DNA extraction methods for use with blood cultures are presented and found to be superior in recovering DNA of Leptospira interrogans when compared with three previously described methods. The improved methods were easy and robust in use with all tested brands of blood culture media. Applied to 96 blood cultures obtained from 36 patients suspected of leptospirosis, all seven patients with positive convalescence serology were found positive by PCR if at least one anaerobic and one aerobic blood culture, sampled before antibiotic therapy were tested. Conclusions/Significance: This study suggests that a specific and early diagnosis can be obtained in most cases of sever
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