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Involvement of Mrs3/4 in Mitochondrial Iron Transport and Metabolism in Cryptococcus neoformans

  • Choi, Yoojeong;Do, Eunsoo;Hu, Guanggan;Caza, Melissa;Horianopoulos, Linda C.;Kronstad, James W.;Jung, Won Hee
    • Journal of Microbiology and Biotechnology
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    • v.30 no.8
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    • pp.1142-1148
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    • 2020
  • Mitochondria play a vital role in iron uptake and metabolism in pathogenic fungi, and also influence virulence and drug tolerance. However, the regulation of iron transport within the mitochondria of Cryptococcus neoformans, a causative agent of fungal meningoencephalitis in immunocompromised individuals, remains largely uncharacterized. In this study, we identified and functionally characterized Mrs3/4, a homolog of the Saccharomyces cerevisiae mitochondrial iron transporter, in C. neoformans var. grubii. A strain expressing an Mrs3/4-GFP fusion protein was generated, and the mitochondrial localization of the fusion protein was confirmed. Moreover, a mutant lacking the MRS3/4 gene was constructed; this mutant displayed significantly reduced mitochondrial iron and cellular heme accumulation. In addition, impaired mitochondrial iron-sulfur cluster metabolism and altered expression of genes required for iron uptake at the plasma membrane were observed in the mrs3/4 mutant, suggesting that Mrs3/4 is involved in iron import and metabolism in the mitochondria of C. neoformans. Using a murine model of cryptococcosis, we demonstrated that an mrs3/4 mutant is defective in survival and virulence. Taken together, our study suggests that Mrs3/4 is responsible for iron import in mitochondria and reveals a link between mitochondrial iron metabolism and the virulence of C. neoformans.

Wnt/$\beta$-catenin/Tcf Signaling Induces the Transcription of a Tumor Suppressor Axin2, a Negative Regulator of the Signaling Pathway

  • Jho, Eek-hoon;Tong Zhang;Claire Domon;Joo, Choun-Ki;Freund, Jean-Noel;Frank Costantini
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.11a
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    • pp.108-108
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    • 2001
  • Axin2/Conductin/Axil and its ortholog Axin are negative regulators of the Wnt signaling pathway, which promote the phosphorylation and degradation of ${\beta}$-catenin. While Axin is expressed ubiquitously, Axin2 mRNA was seen in a restricted pattern during mouse embryogenesis and organogenesis. Because many sites of Axin2 expression overlapped with those of several Wnt genes, we tested whether Axin2 was induced by Wnt signaling. Endogenous Axin2 mRNA and protein expression could be rapidly induced by activation of the Wnt pathway, and Axin2 reporter constructs, containing a 5.6 kb DNA fragment including the promoter and first intron, were also induced. This genomic region contains eight Tcf/LEF consensus binding sites, five of which are located within longer, highly conserved non-coding sequences. The mutation or deletion of these Tcf/LEF sites greatly diminished induction by ${\beta}$-catenin, and mutation of the Tcf/LEF site T2 abolished protein binding in an electrophoretic mobility-shift assay. These results strongly suggest that Axin2 is a direct target of the Wnt pathway, mediated through Tcf/LEF factors. The 5.6 kb genomic sequence was sufficient to direct the tissue specific expression of d2EGFP in transgenic embryos, consistent with a role for the Tcf/LEF sites and surrounding conserved sequences in the in vivo expression pattern of Axin2. Our results suggest that Axin2 participates in a negative feedback loop, which could serve to limit the duration or intensity of a Wnt-initiated signal.

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A molecular investigation of Saccharina sessilis from the Aleutian Islands reveals a species complex, necessitating the new combination Saccharina subsessilis

  • Starko, Samuel;Boo, Ga Hun;Martone, Patrick T.;Lindstrom, Sandra C.
    • ALGAE
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    • v.33 no.2
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    • pp.157-166
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    • 2018
  • Cryptic species complexes are increasingly recognized in phycological research, obscuring taxonomy and raising questions about factors influencing speciation. A recent exploration of kelp genetic diversity on Haida Gwaii, British Columbia revealed the existence of a new species, Saccharina druehlii, which is cryptic with Saccharina sessilis. This suggests that molecular investigations further north may be required to elucidate the taxonomy and evolutionary history of this lineage. Although, for several decades, S. sessilis was considered a single highly variable species, its taxonomy has been far from straightforward. In particular, Hedophyllum subsessile (Areschoug) Setchell is now recognized as a synonym of S. sessilis in North America, but as a growth form of Saccharina bongardiana in Far East Russia. To resolve this taxonomic confusion, we sequenced mitochondrial (CO1-5P) and nuclear (internal transcribed spacer) markers of S. sessilis populations from the Aleutian Islands, Alaska, USA. Interestingly, none of our sequences matched S. sessilis sensu stricto. Instead, CO1-5P sequences from populations in the central and eastern Aleutians matched exactly S. druehlii with increasing sequence divergence occurring westward. Samples from Attu, the western-most island, composed a genetic group that clearly represents Kjellman's concept of Hafgygia bongardiana f. subsessilis and is distinct enough from S. druehlii and S. sessilis to potentially constitute a distinct species. Therefore, Saccharina subsessilis comb. nov. is proposed for this entity. Our results suggest the existence of a species complex at the crown node of S. sessilis and thus further investigation of Saccharina in Alaskan waters should be conducted to reconstruct the evolutionary history of this fascinating lineage.

THE ROLE OF GINSENG DRYING IN THE HARVEST AND POST-HARVEST PRODUCTION SYSTEM FOR AMERICAN GINSENG

  • Bailey W.G.;Dalfsen K.B. van;Guo Y.
    • Proceedings of the Ginseng society Conference
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    • 1993.09a
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    • pp.155-163
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    • 1993
  • An American ginseng(Panax quillquefolium L) industry has emerged in British Columbia, Canada over the past ten years. Interest has grown very rapidly and with this development, attention is now moving away from field production issues and emphasis is being directed to enhancements in ginseng storage, drying and processing. There is a dearth of knowledge on these aspects even though they are crucial to international competitiveness. Enhancement dicatates the application of a systems approach to optimizing the harvest and post - harvest production system(crop digging, pre - washing cold storage. washing, drying and post - drying storage). Research in British Columbia to date has focussed on drying and storage issues and has resulted in the design of an enhanced commercial drying system. The role of dryer management, loading rates, airflow rates and pre - drying cold storage on American ginseng root drying rates and root quality were examined. From the dryer management experiments, there are distinct advantages to size sorting root to yield optimum drying rates. If unsorted root is used, efficiency is increased if the trays are systematically rotated. Loading rate experiments illustrate that increasing rates above those currently used in commercial dryers are possible without any sacrifice in quality. This has significant implications for commercial drying. Pre - drying cold storage is a most significant tool for managing drying operations. Over a period of six weeks, no discernable decrease in quality was found as a consequence of cold storage. Further, the moisture loss and the associated root surface changes(loss of surface soil in storage for example) provide new challenges for root quality management. Continued research and technological innovation will be crucial in addressing the demanding challenges of the future.

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Antiarthritic Activity and Inflammatory Mediators Modulation Effect of Traditional Ajmodadi Churna on Arthritis Experimental Model

  • Vikash Sharma;Shiv Shankar Shukla;Bina Gidwani;Ravindra Kumar Pandey
    • Journal of Pharmacopuncture
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    • v.26 no.3
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    • pp.257-264
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    • 2023
  • Objectives: The study was designed to evaluate anti-arthritic activity of Ajmodadi Churna (AC) and its effect on Complete freund's adjuvant (CFA)-induced arthritis in Wistar rats. Methods: Arthritis was induced by injecting 0.2 mL CFA into sub plantar surface of left hind paw. Test sample AC-1 and AC-2, 200 and 400 mg/kg, respectively was given to the animals for 21 consecutive days. The increase in swelling was observed after induction of arthritis. The paw edema was measured on 0, 3, 7, 14 and 21 day using Vernier caliper after the induction of arthritis. The collected blood samples further used for the estimation of red blood cells (RBC), white blood cells (WBC), erythrocytes sedimentation rate (ESR), and hemoglobin (Hb), using hematology analyzer. Serum concentration of IL-6 and TNF-α were also measured using rat ELISA kits. Results: Results showed that a significant reduction in paw edema was observed in AC-2 treated rats. The paw edema was restored on day 21 was 4.48 mm for AC-2, which is near to the control group. The arthritis score in treated rats was found to be considerably lower than in the control group i.e. 0.83 for AC-2 and 1.50 for AC-1. A decrease in levels of RBC and hemoglobin were observed in arthritic rats. Inflammation was significantly reduced and serum levels of IL-6 and TNF-α were lowered after treatment with the test drug. Conclusion: It can be concluded from the study that AC possess significant anti-arthritic activity. Furthermore, this condition was linked to a reduction in abnormal humoral immune responses.

Cone-beam computed tomographic reconstructions in the evaluation of maxillary impacted canines

  • David MacDonald;Sharifa Alebrahim;Edwin Yen;Jolanta Aleksejuniene
    • Imaging Science in Dentistry
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    • v.53 no.2
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    • pp.145-151
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    • 2023
  • Purpose: Prior to cone-beam computed tomography (CBCT), orthodontic competence included radiological interpretation. Nevertheless, maxillary impacted canines (MICs), because of their position and adjacent complex anatomy, have been challenging to interpret, particularly with regard to root resorption. Although CBCT cross-sectional reconstructions of MICs yielded clearer insights into its diagnosis and treatment planning, the value of simultaneously using 2 different cross-sectional or multiplanar reconstructions of the CBCT datasets - orthogonal and curved/panoramic multiplanar reconstructions - has hitherto not been considered. Materials and Methods: Both orthogonal and curved/panoramic multiplanar reconstruction series of 5 screenshots were each reconstructed from the 5 cm×5 cm CBCT datasets of 15 separate MICs. Fifteen credentialled and experienced orthodontist volunteers reviewed 2 separate PowerPoints of 15 randomized series each, 1 week apart. Their review considered 6 factors that could affect treatment: the position and level of the MIC, the presence or absence of root resorption, ankylosis, cysts, and dilaceration. Results: All 15 orthodontists were statistically similar regarding overall years of experience and of CBCT use. Although either reconstruction alone allowed the orthodontists to determine whether ankylosis and, to a lesser extent, most of the other features were present or absent in the MIC, reviewing both reconstructions together was necessary to determine whether root resorption was present or absent in the adjacent tooth. Conclusion: Reviewing both orthogonal and curved/panoramic multiplanar reconstructions was necessary to evaluate the presence or absence of root resorption in the teeth adjacent to MICs and that of many other features.

Systematizing Information Use to Address Determinants of Health Worker Health in South Africa: A Cross-sectional Mixed Method Study

  • Muzimkhulu Zungu;Annalee Yassi ;Jonathan Ramodike;Kuku Voyi;Karen Lockhart;David Jones;Spo Kgalamono;Nkululeko Thunzi;Jerry Spiegel
    • Safety and Health at Work
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    • v.14 no.4
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    • pp.368-374
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    • 2023
  • Background: Recognizing that access to safe and healthy working conditions is a human right, the World Health Organization (WHO) calls for specific occupational safety and health (OSH) programs for health workers (HWs). The WHO health systems' building blocks, and the International Labour Organization (ILO), highlight the importance of information as part of effective systems. This study examined how OSH stakeholders access, use, and value an occupational health information system (OHIS). Methods: A cross-sectional survey of OSH stakeholders was conducted as part of a larger quasi experimental study in four teaching hospitals. The study hospitals and participants were purposefully selected and data collected using a modified questionnaire with both closed and open-ended questions. Quantitative analysis was conducted and themes identified for qualitative analysis. Ethics approval was provided by the University of Pretoria and University of British Columbia. Results: There were 71 participants comprised of hospital managers, health and safety representatives, trade unions representatives and OSH professionals. At least 42% reported poor accessibility and poor timeliness of OHIS for decision-making. Only 50% had access to computers and 27% reported poor computer skills. When existing, OHIS was poorly organized and needed upgrades, with 85% reporting the need for significant reforms. Only 45% reported use of OHIS for decision-making in their OSH role. Conclusion: Given the gap in access and utilization of information needed to protect worker's rights to a safe and healthy workplace, more attention is warranted to OHIS development and use as well as education and training in South Africa and beyond.

Quality of Mountain Pine Beetle Infested Fibers: Implications on the Production of Pulp and Paper Products

  • Kim, Yong-Sik;Obermajer, Alice;Korehei, Reza;Kadla, John F.;Yoon, Byung-Ho
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.41 no.1
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    • pp.1-8
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    • 2009
  • Mountain Pine Beetle (MPB) attacked pine was evaluated for pulp quality, chemical and physical properties, and bleachability. Chemical analyses showed that the dehydroabietic acid and total acetone extractives content were higher in the year 3 (grey) attacked MPB chips and lower in the year 5 (grey) attacked MPB chips as compared to a typical SPF (spruce/pine/fir) reference. Lignin and carbohydrate content of the MPB wood chips were comparable to the SPF. Similarly, there was little difference in kappa number, pulp yield and liquor consumption between the 3 and 5 year MPB attacked wood. Likewise there was no significant difference in the resulting tear strength, burst, or tensile strength. There appeared to be an improved bleaching response in the MPB attacked pulp as compared to the SPF reference, but this was accompanied by a slightly lower bleached pulp yield and higher bleach filtrate COD and solids content.

A Review Study on Interprofessional College Education in Health Care Sector (보건의료분야 전문가간 대학 교육에 대한 사례연구)

  • Yoon, Byoung-Jun;Lee, Jun-Hyup
    • The Journal of Korean Society for School & Community Health Education
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    • v.11 no.1
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    • pp.149-158
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    • 2010
  • Background & Objectives: Rising concerns about patient safety and looming health provider shortages were generating new recognition for an old idea. Interprofessional education means that two or more professions learn with, from and about other to improve collaboration and the quality of healthcare. The University of British Columbia established the College of Health Disciplines in 2001 to examine the merits of interprofessional health education. The objective of this study was to review UBC's interprofessional health education and to introduce the theoretical framework of interprofessional education for collaborative patient-centered practice. Methods: This study was conducted with the materials relevant to the interprofessional education. We reviewed the journals and Web site for this subject and we obtained interview data from administrators in the University of British Columbia, College of Health Disciplines. Results: We introduced interdisciplinary education for collaborative patient-centered practice model. It is assumed valuable model in preparing the interprofessional education as well as theoretical framework for implementation. We preseuted the example for interprofessional education of the College of Health Disciplines, University of British Columbia. Conclusion: We need to introduce the interprofessional education at the health care departments of University or College in Korea.

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