BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

THE JOURNAL OF BIOLOGICAL CHEMISTRY: The Biochemical Behavior of LeadL I. Influence of Calcium, Phosphorus, and Vitamin D on Lead in Blood and Bone

Background
The internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA is regarded as one of the candidate DNA barcodes because it possesses a number of valuable characteristics, such as the availability of conserved regions for designing universal primers, the ease of its amplification, and sufficient variability to distinguish even closely related species. However, a general analysis of its ability to discriminate species in a comprehensive sample set is lacking.

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Use of ITS2 Region as the Universal DNA Barcode for Plants and Animals

Fascioliasis, caused by liver fluke species of the genus Fasciola, has always been well recognized because of its high veterinary impact but it has been among the most neglected diseases for decades with regard to human infection. However, the increasing importance of human fascioliasis worldwide has re‐launched interest in fascioliasis. From the 1990s, many new concepts have been developed regarding human fascioliasis and these have furnished a new baseline for the human disease that is very different to a simple extrapolation from fascioliasis in livestock. Studies have shown that human fascioliasis presents marked heterogeneity, including different epidemiological situations and transmission patterns in different endemic areas. This heterogeneity, added to the present emergence/re‐emergence of the disease both in humans and animals in many regions, confirms a worrying global scenario. The huge negative impact of fascioliasis on human communities demands rapid action. When analyzing how better to define control measures for endemic areas differing at such a level, it would be useful to have genetic markers that could distinguish each type of transmission pattern and epidemiological situation. Accordingly, this chapter covers aspects of aetiology, geographical distribution, epidemiology, transmission and control in order to obtain a solid baseline for the interpretation of future results. The origins and geographical spread of F. hepatica and F. gigantica in both the ruminant pre‐domestication times and the livestock post‐domestication period are analyzed. Paleontological, archaeological and historical records, as well as genetic data on recent dispersal of livestock species, are taken into account to establish an evolutionary framework for the two fasciolids across all continents. Emphasis is given to the distributional overlap of both species and the roles of transportation, transhumance and trade in the different overlap situations. Areas with only one Fasciola spp. are distinguished from local and zonal overlaps in areas where both fasciolids co‐exist. Genetic techniques applied to liver flukes in recent years that are useful to elucidate the genetic characteristics of the two fasciolids are reviewed. The intra‐specific and inter‐specific variabilities of ‘pure’ F. hepatica and ‘pure’ F. gigantica were ascertained by means of complete sequences of ribosomal deoxyribonucleic acid (rDNA) internal transcribed spacer (ITS)‐2 and ITS‐1 and mitochondrial deoxyribonucleic acid (mtDNA) cox1 and nad1 from areas with only one fasciolid species. Fasciolid sequences of the same markers scattered in the literature are reviewed. The definitive haplotypes established appear to fit the proposed global evolutionary scenario. Problems posed by fasciolid cross‐breeding, introgression and hybridization in overlap areas are analyzed. Nuclear rDNA appears to correlate with adult fluke characteristics and fasciolid/lymnaeid specificity, whereas mtDNA does not. However, flukes sometimes appear so intermediate that they cannot be ascribed to either F. hepatica‐like or F. gigantica‐like forms and snail specificity may be opposite to the one deduced from the adult morphotype. The phenotypic characteristics of adults and eggs of ‘pure’ F. hepatica and F. gigantica, as well as of intermediate forms in overlap areas, are compared, with emphasis on the definitive host influence on egg size in humans. Knowledge is sufficient to support F. hepatica and F. gigantica as two valid species, which recently diverged by adaptation to different pecoran and lymnaeid hosts in areas with differing environmental characteristics. Their phenotypic differences and ancient pre‐domestication origins involve a broad geographical area that largely exceeds the typical, more local scenarios known for sub‐species units. Phenomena such as abnormal ploidy and aspermic parthenogenesis in hybrids suggest that their separate evolution in pre‐domestication times allowed them to achieve almost total genetic isolation. Recent sequencing results suggest that present assumptions on fasciolid‐lymnaeid specificity might be wrong. The crucial role of lymnaeids in fascioliasis transmission, epidemiology and control was the reason for launching a worldwide lymnaeid molecular characterization initiative. This initiative has already furnished useful results on several continents. A standardized methodology for fasciolids and lymnaeids is proposed herein in order that future work is undertaken on a comparable basis. A complete understanding of molecular epidemiology is expected to help greatly in designing global actions and local interventions for control of fascioliasis.

Chapter 2. Fasciola, lymnaeids and human fascioliasis, with a global overview on disease transmission, epidemiology, evolutionary genetics, molecular epidemiology and control.

Organotin(IV)n+ complexes formed with biologically active ligands: equilibrium and structural studies, and some biological aspects

The multifaceted role of glutathione S-transferases in cancer

Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent.

The tripeptide glutathione (GSH) is the most abundant intracellular nonprotein thiol, and it is involved in many cellular functions including redox-homeostatic buffering. Cellular radiosensitivity has been shown to be inversely correlated to the endogenous level of GSH. On the other hand, controversy is raised with respect to its role in the field of radioprotection since GSH failed to provide consistent protection in several cases. Reports have been published that DNA repair in cells has a dependence on GSH. Subsequently, S-glutathionylation (forming mixed disulfides with the protein–sulfhydryl groups), a potent mechanism for posttranslational regulation of a variety of regulatory and metabolic proteins when there is a change in the celluar redox status (lower GSH/GSSG ratio), has received increased attention over the last decade. GSH, as a single agent, is found to affect DNA damage and repair, redox regulation and multiple cell signaling pathways. Thus, seemingly, GSH does not only act as a radioprotector against DNA damage induced by X-rays through glutathionylation, it may also act as a modulator of the DNA-repair activity. Judging by the number of publications within the last six years, it is obvious that the field of protein glutathionylation impinges on many aspects of biology, from regulation of protein function to roles of cell cycle and apoptosis. Aberrant protein glutathionylation and its association with cancer and other diseases is an area of increasing interest.

https://www.mdpi.com/2072-6643/5/2/525/pdf

Reduced Glutathione: A Radioprotector or a Modulator of DNA-Repair Activity?

The mutagenic and carcinogenic potency of betel-nut components is well established. This study was undertaken to determine the genotoxic potency of an aqueous extract of raw betel nut (AEBN) in relation to the endogenous glutathione (GSH) level in mouse bone marrow cells (BMC) and human peripheral blood lymphocytes (PBLs), and to find out whether arecoline (ARC), an alkaloid of betel nut, could generate reactive oxygen species (ROS) in these cells. It was observed that AEBN has genotoxic properties, which is further enhanced by depletion of endogenous GSH levels. However, the degree of enhancement varies with the type of parameter and cell system studied. The present data indicate that the generation of ROS by ARC could partially contribute to the induction of chromosomal aberrations (CAs), since the frequency of ARC-induced CAs was reduced either by post-treatment with superoxide dismutase (SOD) or in anoxic conditions. However, the induction of sister chromatid exchanges (SCEs) probably involves p53-dependent changes in cell proliferation and allowing some repair of DNA damage. The extent of damage for each parameter was higher when the mice were exposed to AEBN for 30 days than 5 days. Longer exposure showed higher level of p53 expression in mouse BMC, which could block the damaged cells from proliferation and allow the cells to repair the DNA damage.

Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells.

Previous functional and deletion mapping studies on cervical cancer (CC) have implicated one or more tumor suppressor genes (TSGs) on chromosome 11 at q13 and q22–24 regions. Of these, the 11q22–24 region exhibits frequent allelic deletions in a variety of solid tumor types, suggesting the presence of critical genes for tumor suppression in this region. However, the precise region of deletion on 11q is not clearly defined in CC. In an attempt to accurately map the deleted region, we performed an extensive loss of heterozygosity (LOH) mapping in 58 tumors using 25 polymorphic loci on both the short and long arms. The pattern of LOH identified three sites of deletions, two on 11p (p15.11–p15.3 and p12–13), and one on 11q (q23.1–q23.2). The 11q23.1–q23.2 exhibited highest frequency (60.6%) of deletions, suggesting that this could be the site of a candidate TSG in CC. The minimal deletion at 11q23.1–23.2 was restricted to a 6-cM region between 123.5 and 129.5 cM genetic distance on chromosome 11, identifying the site of a potential TSG important in the pathogenesis of CC. At least five known genes and 28 UniGene clusters were mapped to the present commonly deleted region. In addition, we have excluded a previously known TSG PPP2R1B at 11q23 as a deletion target in CC. The definition of the minimal deletion and the availability of expressed sequence resources should facilitate the identification of the candidate TSG.

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Anupam Chatterjee

Papers

The multifaceted role of glutathione S-transferases in cancer

Bio-synthesis of silver nanoparticles using Potentilla fulgens Wall. ex Hook. and its therapeutic evaluation as anticancer and antimicrobial agent.

Reduced Glutathione: A Radioprotector or a Modulator of DNA-Repair Activity?

Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells.

Identification of a 6-cM Minimal Deletion at 11q23.1–23.2 and Exclusion of PPP2R1B Gene as a Deletion Target in Cervical Cancer