Browse publications by year: 2016

  1. Froufe E, Gan HM, Lee YP, Carneiro J, Varandas S, Teixeira A, et al.
    PMID: 27158872 DOI: 10.3109/19401736.2015.1074223
    Freshwater mussels of the family Unionidae exhibit a particular form of mitochondria inheritance called double uniparental inheritance (DUI), in which the mitochondria are inherited by both male and female parents. The (M)ale and (F)emale mitogenomes are highly divergent within species. In the present study, we determine and describe the complete M and F mitogenomes of the Endangered freshwater mussel Potomida littoralis (Cuvier, 1798). The complete M and F mitogenomes sequences are 16 451 bp and 15 787 bp in length, respectively. Both F and M have the same gene content: 13 protein-coding genes (PCGs), 22 transfer RNA (trn) and 2 ribosomal RNA (rrn) genes. Bayesian analyses based on the concatenated nucleotide sequences of 12 PCGs and 2 rrn genes of both genomes, including mitogenome sequences available from related species, were performed. Male and Female lineages are monophyletic within the family, but reveal distinct phylogenetic relationships.
    MeSH terms: Animals; DNA, Mitochondrial/genetics; DNA, Mitochondrial/isolation & purification; Female; Fresh Water; Male; Mitochondria/genetics; Phylogeny; RNA, Transfer/genetics; Open Reading Frames; Bivalvia/genetics*; Genes, Mitochondrial; Genome, Mitochondrial*; Endangered Species*
  2. Ten Bosch QA, Singh BK, Hassan MR, Chadee DD, Michael E
    PLoS Negl Trop Dis, 2016 05;10(5):e0004680.
    PMID: 27159023 DOI: 10.1371/journal.pntd.0004680
    The epidemiology of dengue fever is characterized by highly seasonal, multi-annual fluctuations, and the irregular circulation of its four serotypes. It is believed that this behaviour arises from the interplay between environmental drivers and serotype interactions. The exact mechanism, however, is uncertain. Constraining mathematical models to patterns characteristic to dengue epidemiology offers a means for detecting such mechanisms. Here, we used a pattern-oriented modelling (POM) strategy to fit and assess a range of dengue models, driven by combinations of temporary cross protective-immunity, cross-enhancement, and seasonal forcing, on their ability to capture the main characteristics of dengue dynamics. We show that all proposed models reproduce the observed dengue patterns across some part of the parameter space. Which model best supports the dengue dynamics is determined by the level of seasonal forcing. Further, when tertiary and quaternary infections are allowed, the inclusion of temporary cross-immunity alone is strongly supported, but the addition of cross-enhancement markedly reduces the parameter range at which dengue dynamics are produced, irrespective of the strength of seasonal forcing. The implication of these structural uncertainties on predicted vulnerability to control is also discussed. With ever expanding spread of dengue, greater understanding of dengue dynamics and control efforts (e.g. a near-future vaccine introduction) has become critically important. This study highlights the capacity of multi-level pattern-matching modelling approaches to offer an analytic tool for deeper insights into dengue epidemiology and control.
    MeSH terms: Computer Simulation; Dengue/immunology; Dengue/epidemiology*; Dengue/prevention & control*; Dengue Virus/classification*; Humans; Models, Biological*; Pattern Recognition, Automated*; Seasons*; Trinidad and Tobago/epidemiology; Serogroup
  3. Patmanathan SN, Johnson SP, Lai SL, Panja Bernam S, Lopes V, Wei W, et al.
    Sci Rep, 2016 05 10;6:25650.
    PMID: 27160553 DOI: 10.1038/srep25650
    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
    MeSH terms: Fingolimod Hydrochloride; Carcinoma, Squamous Cell; Cisplatin; Lysophospholipids; Mouth Mucosa; Mouth Neoplasms; RNA, Messenger; Sphingosine; Signal Transduction; Up-Regulation; Cell Death; Apoptosis; Molecular Targeted Therapy
  4. Johari K, Saman N, Song ST, Cheu SC, Kong H, Mat H
    Chemosphere, 2016 Aug;156:56-68.
    PMID: 27160635 DOI: 10.1016/j.chemosphere.2016.04.114
    In this study, chars from coconut pith (CP) were prepared aiming for superior adsorption towards elemental mercury (Hg(o)). The yield, proximate analysis, textural characteristics, surface functional groups and elemental composition analyses of the chars produced at pyrolysis temperature of 300 °C, 500 °C, 700 °C and 900 °C were compared. The surface area, pore volume, ash and carbon content of chars increased, while the yield and moisture content decreased with increasing pyrolysis temperatures. The changing of physical and chemical properties of the chars produced at variety pyrolysis temperature was much effect on the Hg(o) adsorption performance and definitely provides important information on the Hg(o) adsorption mechanism. The highest Hg(o) adsorption capacity was observed for CP900 (6067.49 μg/g), followed by CP700 (2395.98 μg/g), CP500 (289.76 μg/g), CP300 (1.68 μg/g), and CP (0.73 μg/g). The equilibrium data were well described by the Freundlich adsorption isotherm model. The pseudo-second order best described the kinetic data of the Hg(o) adsorption onto CP and CP300. For chars produced at higher pyrolysis temperature, however, the pseudo-zero order and pseudo-second order fitted well for the adsorption and breakthrough regions, respectively. The Hg(o) adsorption capacity of chars obtained from high pyrolysis temperature of CP significantly outperformed the commercial activated carbon (Darco KB-B) as well as superior to chars reported in the literature indicating the CP can be used as a precursor for preparation of chars as elemental mercury adsorbents.
    MeSH terms: Adsorption; Air Pollutants/chemistry*; Charcoal/chemistry*; Cocos*; Hot Temperature; Kinetics; Mercury/chemistry*; Plant Stems
  5. Al-Ta'ii HM, Amin YM, Periasamy V
    Sci Rep, 2016 May 10;6:25519.
    PMID: 27160654 DOI: 10.1038/srep25519
    Deoxyribonucleic acid or DNA based sensors, especially as humidity and alpha particle sensors have become quite popular in recent times due to flexible and highly optimizable nature of this fundamental biomaterial. Application of DNA electronics allow for more sensitive, accurate and effective sensors to be developed and fabricated. In this work, we examined the effect of different humidity conditions on the capacitive and resistive response of Aluminum (Al)/DNA/Al Schottky barrier structure when bombarded by time-dependent dosages of alpha particles. Based on current-voltage profiles, which demonstrated rectifying behaviours, Schottky diode parameters such as ideality factor, barrier height and series resistance was calculated. Results observed generally pointed towards a decrease in the resistance value from the pristine to the radiated structures. It was also demonstrated that under the effect of humidity, the capacitance of the DNA thin film increased from 0.05894 to 92.736 nF, with rising relative humidity level. We also observed the occurrence of the hypersensitivity phenomena after alpha irradiation between 2 to 4 min by observing a drop in the series resistance, crucial in the study of DNA damage and repair mechanisms. These observations may also suggest the exciting possibility of utilizing Al/DNA/Al Schottky diodes as potentially sensitive humidity sensors.
  6. M Didi AL, Azman RR, Nazri M
    Leg Med (Tokyo), 2016 May;20:49-52.
    PMID: 27161924 DOI: 10.1016/j.legalmed.2016.04.002
    PURPOSE: The use of Multi Detector Computed Tomography (MDCT) volume measurements of bones for sex determination allows fragile, fragmented human remains to be assessed without compromising the specimen. We set out to assess the ability of MDCT carpal bone volume measurement in determining sex in a Malaysian population.

    MATERIALS AND METHODS: 52 healthy volunteers were scanned in a 16-slice MDCT, and the volume of 104 sets of carpal bones was measured using a Syngo workstation (Both CT and workstation-Siemens Healthcare, Erlangen, Germany).

    RESULTS: Male carpal bones were of higher volume compared to the female carpal bones (p<0.001). Area under the curve (AUC) assessment of responder-operator characteristics curves showed that the trapezium bone was best able to predict sex with an AUC of 0.986. At a trapezium bone volume of ⩾1.94cm(3), there was a 93.5% probability that the subject was male. Binary logistic regression analysis found that the highest accuracy was derived using the pisiform, trapezium and capitate bones. There was a strong relationship between sex prediction and grouping of the carpal bone volumes (Nagelkerke R(2)=0.923) with an overall prediction accuracy of 97%.

    CONCLUSION: All 8 carpal bones exhibit sexual dimorphism to varying degrees. A binary regression analysis combining the 5 carpal bones with the highest predictive values for sex produces an accurate predictive model.

    MeSH terms: Adolescent; Adult; Carpal Bones*; Female; Humans; Malaysia; Male; Sex Factors; Forensic Anthropology; Sex Determination by Skeleton/methods*; Multidetector Computed Tomography*
  7. Lee WC, Khoo BE, Abdullah AFL
    Sci Justice, 2016 May;56(3):201-209.
    PMID: 27162018 DOI: 10.1016/j.scijus.2016.01.001
    Background correction algorithm (BCA) is useful in enhancing the visibility of images captured in crime scenes especially those of untreated bloodstains. Successful implementation of BCA requires all the images to have similar brightness which often proves a problem when using automatic exposure setting in a camera. This paper presents an improved background correction algorithm (BCA) that applies mean-based contrast adjustment as a pre-correction step to adjust the mean brightness of images to be similar before implementing BCA. The proposed modification, namely mean-based adaptive BCA (mABCA) was tested on various image samples captured under different illuminations such as 385 nm, 415 nm and 458 nm. We also evaluated mABCA of two wavelengths (415 nm and 458 nm) and three wavelengths (415 nm, 380 nm and 458 nm) in enhancing untreated bloodstains on different surfaces. The proposed mABCA is found to be more robust in processing images captured in different brightness and thus overcomes the main issue faced in the original BCA.
    MeSH terms: Algorithms*; Blood Stains*; Dermatoglyphics*; Humans; Image Enhancement/methods*; Image Processing, Computer-Assisted; Photography*
  8. Britton S, Cheng Q, Grigg MJ, William T, Anstey NM, McCarthy JS
    Am J Trop Med Hyg, 2016 07 06;95(1):120-2.
    PMID: 27162264 DOI: 10.4269/ajtmh.15-0670
    The simian parasite Plasmodium knowlesi is now the commonest cause of malaria in Malaysia and can rapidly cause severe and fatal malaria. However, microscopic misdiagnosis of Plasmodium species is common, rapid antigen detection tests remain insufficiently sensitive and confirmation of P. knowlesi requires polymerase chain reaction (PCR). Thus available point-of-care diagnostic tests are inadequate. This study reports the development of a simple, sensitive, colorimetric, high-throughput loop-mediated isothermal amplification assay (HtLAMP) diagnostic test using novel primers for the detection of P. knowlesi. This assay is able to detect 0.2 parasites/μL, and compared with PCR has a sensitivity of 96% for the detection of P. knowlesi, making it a potentially field-applicable point-of-care diagnostic tool.
    MeSH terms: Animals; Haplorhini/parasitology; Colorimetry; Diagnostic Tests, Routine; Humans; Malaria/diagnosis*; Malaysia; Sensitivity and Specificity; Plasmodium knowlesi/genetics; Plasmodium knowlesi/isolation & purification*; DNA Primers/genetics; Point-of-Care Systems; Nucleic Acid Amplification Techniques/methods*; High-Throughput Nucleotide Sequencing/methods*
  9. Jafarzadeh S, Alias AK, Ariffin F, Mahmud S, Najafi A
    J Food Sci Technol, 2016 Feb;53(2):1111-9.
    PMID: 27162391 DOI: 10.1007/s13197-015-2017-7
    Effects of nano-kaolin incorporation into semolina films on the physical, mechanical, thermal, barrier and antimicrobial properties of the resulting bio-nanocomposite films were investigated. The properties included crystal structure (by X-ray diffraction), mechanical resistance, color, Fourier transform infrared spectra, decomposition temperature, water-vapor permeability (WVP), oxygen permeability (OP), and antimicrobial activity against Staphylococcus aureus and Escherichia coli. Kaolin was incorporated into biofilms at various amounts (1, 2, 3, 4, and 5 %, w/w total solid). All films were plasticized with 50 % (w/w total solid) combination of sorbitol/glycerol at 3:1 ratio. The incorporation of nanokaolin into semolina films decreased OP and WVP. The moisture content and water solubility of the films were found to decrease by nanokaolin reinforcement, and mechanical properties of films were improved by increasing nanokaolin concentration. Tensile strength and Young's modulus increased from 3.41 to 5.44 MPa and from 63.12 to 136.18, respectively, and elongation-at-break decreased. The films did not exhibit UV absorption. In conclusion, nanokaolin incorporation enhanced the barrier and mechanical properties of semolina films, indicating the potential application of these bio-nanocomposites in food-product packaging.
  10. Gan KB, Yahyavi ES, Ismail MS
    Technol Health Care, 2016 Sep 14;24(5):761-8.
    PMID: 27163300 DOI: 10.3233/THC-161161
    BACKGROUND: At the emergency triage center, assessment of the present of the danger signs and measurement of vital signs are measured according to the guidelines. The respiration rate is still posing a challenge to the doctor as it is impractical to use conventional devices. Attaching measurement devices to the patient will induce artificial measurements (self-awareness stress effects) besides being time-consuming. Currently, the medical officers visually count the number of times the chest movement in a minute, sometimes poses cultural challenges especially for female patients.

    OBJECTIVE: The main objective of this paper is to develop a robust algorithm to extract respiration rate using the contactless displacement sensor.

    METHODS: In this study, chest movements were used as an indicative of inspiration and expiration to measure respiratory rate using the contactless displacement sensor. The contactless optical signals were recorded from 32 healthy subjects in four different controlled breathing conditions: rest, coughing, talking and hand movement to obtain the motion artifacts that the patients may have in the emergency department. The Empirical mode decomposition (EMD) algorithm was used to derive continuous RR signal from the contactless optical signal.

    RESULTS: The analysis showed that there is a good correlation (0.9702) with RMSE of 0.33 breaths per minutes between the contact respiration rate and contactless respiration rate using empirical mode decomposition method.

    CONCLUSION: It can be concluded that the empirical mode decomposition method can extract the respiration rate of the contactless optical signal from chest movement.

    MeSH terms: Adult; Algorithms*; Female; Fourier Analysis; Humans; Lasers*; Male; Middle Aged; Respiratory Function Tests/instrumentation*; Thorax/physiology*; Respiratory Rate/physiology*
  11. Saeedi P, Skeaff SA, Wong JE, Skidmore PM
    Nutrients, 2016;8(5).
    PMID: 27164137 DOI: 10.3390/nu8050271
    The aim of this study was to assess the reproducibility and validity of a non-quantitative 28-item food frequency questionnaire (FFQ). Children aged 9-10 years (n = 50) from three schools in Dunedin, New Zealand, completed the FFQ twice and a four-day estimated food diary (4DEFD) over a two-week period. Intraclass correlation coefficients (ICC) and Spearman's correlation coefficients (SCC) were used to determine reproducibility and validity of the FFQ, respectively. Weekly intakes were estimated for each food item and aggregated into 23 food items/groups. More than half of the food items/groups (52.2%) had an ICC ≥0.5. The median SCC between FFQ administrations was 0.66 (ranging from 0.40 for processed meat to 0.82 for sweets and non-dairy drinks). Cross-classification analysis between the first FFQ and 4DEFD for ranking participants into thirds showed that breakfast cereals had the highest agreement (54.0%) and pasta the lowest (34.0%). In validity analyses, 70% of food items/groups had a SCC ≥0.3. Results indicate that the FFQ is a useful tool for ranking children according to food items/groups intake. The low respondent burden and relative simplicity of the FFQ makes it suitable for use in large cohort studies of 9-10 year-old children in New Zealand.
    MeSH terms: Edible Grain; Child; Diet Surveys; Humans; Meat; New Zealand; Reproducibility of Results; Cohort Studies; Diet Records; Breakfast
  12. Gronemeyer T, Suarez W, Nuytemans H, Calaramo M, Wistuba A, Mey FS, et al.
    Plants (Basel), 2016;5(2).
    PMID: 27164153 DOI: 10.3390/plants5020023
    With 50 species of the genus Nepenthes L. currently described from the Philippines, it is without doubt that the country, along with the islands of Sumatra (Indonesia) and Borneo (Indonesia, Malaysia, Brunei), should be considered the center of diversity of the genus. In this work, we describe two new species. One species, N. aenigma sp. nov., is from Ilocos Norte province on Luzon Island and has the-for Nepenthes-unusual ecological preference to grow in dense vegetation in deep shade. The other new species is from Mount Hamiguitan in Davao Oriental province on Mindanao Island. With this new entry, Mount Hamiguitan is now home to four endemic species (N. peltata, N. micramphora, N. hamiguitanensis, N. justinae sp. nov.). Furthermore, we provide an emended description of N. ramos based on field data. Nepenthes kurata is synonymized here with N. ramos.
    MeSH terms: Animals; Biological Phenomena; Borneo; Brunei; Indonesia; Malaysia; Philippines; Islands
  13. Shamsudin NAA, Swamy BPM, Ratnam W, Sta Cruz MT, Sandhu N, Raman AK, et al.
    Rice (N Y), 2016 Dec;9(1):21.
    PMID: 27164982 DOI: 10.1186/s12284-016-0093-6
    BACKGROUND: With the objective of improving the grain yield (GY) of the Malaysian high quality rice cultivar MRQ74 under reproductive stage drought stress (RS), three drought yield QTLs, viz. qDTY 2.2, qDTY 3.1 , and qDTY 12.1 were pyramided by marker assisted breeding (MAB). Foreground selection using QTL specific markers, recombinant selection using flanking markers, and background selections were performed in every generation. BC1F3 derived pyramided lines (PLs) with different combinations of qDTY 2.2, qDTY 3.1 , and qDTY 12.1 were evaluated under both RS and non-stress (NS) during the dry season (DS) of 2013 and 2014 at IRRI.

    RESULTS: The GY reductions in RS trials compared to NS trials ranged from 79 to 99 %. Plant height (PH) was reduced and days to flowering (DTF) was delayed under RS. Eleven BC1F5 MRQ74 PLs with yield advantages of 1009 to 3473 kg ha(-1) under RS and with yields equivalent to MRQ74 under NS trials were identified as promising drought tolerance PLs. Five best PLs, IR 98010-126-708-1-4, IR 98010-126-708-1-3, IR 98010-126-708-1-5, IR 99616-44-94-1-1, and IR 99616-44-94-1-2 with a yield advantage of more than 1000 kg ha(-1) under RS and with yield potential equivalent to that of MRQ74 under NS were selected. The effect of three drought grain yield QTLs under RS in MRQ74 was validated. Under NS, PLs with two qDTY combinations (qDTY 2.2 + qDTY 12.1 ) performed better than PLs with other qDTY combinations, indicating the presence of a positive interaction between qDTY 2.2 and qDTY 12.1 in the MRQ74 background.

    CONCLUSION: Drought tolerant MRQ74 PLs with a yield advantage of more than 1000 kg ha(-1) under RS were developed. Differential yield advantages of different combinations of the qDTYs indicate a differential synergistic relationship among qDTYs.

  14. Singh H, Shimojima M, Fukushi S, Fukuma A, Tani H, Yoshikawa T, et al.
    PMID: 27165561 DOI: 10.1038/emi.2016.35
    Pteropine orthoreovirus (PRV), potentially of bat origin, is reported to be a causative agent of emerging respiratory tract infections among humans in Southeast Asia. We evaluated the efficacy of serologic assays using the major outer capsid and cell attachment proteins (CAP) of PRV strains in the screening, confirmation and identification of three groups of human PRV infections; Indonesian/Japanese, Indonesian/Hong Kong and Malaysian strains. The different serologic assays were tested using rabbit polyclonal antisera raised against these proteins of selected PRV strains, and validation was carried out using sera from a Miyazaki-Bali/2007 PRV-infected patient and the patient's contacts. The results of this study showed that rabbit polyclonal antisera raised against the CAP of the Miyazaki-Bali/2007 PRV strain showed the highest reactivity to the Miyazaki-Bali/2007 PRV and to a lesser extent, cross-reactivity with the HK23629/07 and Melaka PRVs, respectively. Neutralization activity against the Miyazaki-Bali/2007 PRV was observed using rabbit anti-Miyazaki-Bali/2007 PRV CAP (320) but not with rabbit anti-HK23629/07 (<20) and Melaka (<20) PRV CAP. This lack of cross-neutralization, suggests the potential for human reinfection with different strains. The use of sera collected from contacts of the Miyazaki-Bali/2007 PRV-infected patient suggested that human-to-human infections with PRV are unlikely. Previously reported cases of PRV infections among human have been mild. However, the expanding geographic distribution of these viruses, of which its virulence remains unknown, warrants close monitoring to enable the development of prevention and control strategies in the event that a change in virulence occurs.
  15. Adekoya AA, Ahmad S, Maziah M
    Pak J Pharm Sci, 2016 May;29(3):979-84.
    PMID: 27166542
    The use of herbal medicine and traditional healing practices for diagnosis, treatment and prevention of illness and ailment continue to have more awareness among the scientific community due to their safety and also as a source of alternatives to synthetic products. This research assessed the total phenolic compounds and in vitro total antioxidant potentials of water extracts in selected species of Zingiberaceae rhizomes use as spice, drinks and medicine. DPPH and FRAP were used to determine the antioxidant capacity, total flavonoid, phenolic acids and polyphenol contents assays to evaluate the quality of the antioxidant activity and the control was ascorbic acid. The results showed that all extracts contain significant antioxidant activity with Zingiber officinale having the highest activity in all assays. DPPH (222.30mg/TE/g DW), FRAP (98.04mg/TE/g DW), Flavonoid (38.58mg/NGN/g DW) phenolic acid (10.78mg/GAE/g DW) and polyphenols (22.84mg/GAE/g DW). Significant and positive linear correlation were found in DPPH, FRAP and total flavonoid, phenolic acids and polyphenol contents. This study reveals some phytochemicals present in Zingiberaceae species, which might be responsible for their biological activities and reason for it use in folkloric medicine in Southeast Asia.
  16. Kim M, Jung JH, Jin Y, Han GM, Lee T, Hong SH, et al.
    Mar Pollut Bull, 2016 Jul 15;108(1-2):281-8.
    PMID: 27167134 DOI: 10.1016/j.marpolbul.2016.04.049
    The molecular composition and distribution of sterols were investigated in the East China Sea to identify the origins of suspended particulate matter (SPM) in offshore waters influenced by Changjiang River Diluted Water (CRDW). Total sterol concentrations ranged from 3200 to 31,900pgL(-1) and 663 to 5690pgL(-1) in the particulate and dissolved phases, respectively. Marine sterols dominated representing 71% and 66% in the particulate and dissolved phases, respectively. Typical sewage markers, such as coprostanol, were usually absent at ~250km offshore. However, sterols from allochthonous terrestrial plants were still detected at these sites. A negative relationship was observed between salinity and concentrations of terrestrial sterols in SPM, suggesting that significant amounts of terrestrial particulate matter traveled long distance offshore in the East China Sea, and the Changjiang River Diluted Water (CRDW) was an effective carrier of land-derived particulate organic matter to the offshore East China Sea.
    MeSH terms: China; Environmental Monitoring/methods*; Seawater/chemistry*; Sterols/analysis*; Water Pollutants, Chemical/analysis*; Ecosystem; Rivers/chemistry*; Particulate Matter/analysis*; Salinity
  17. Wu YS, Looi CY, Subramaniam KS, Masamune A, Chung I
    Oncotarget, 2016 Jun 14;7(24):36719-36732.
    PMID: 27167341 DOI: 10.18632/oncotarget.9165
    Pancreatic stellate cells (PSC), a prominent stromal cell, contribute to the progression of pancreatic ductal adenocarcinoma (PDAC). We aim to investigate the mechanisms by which PSC promote cell proliferation in PDAC cell lines, BxPC-3 and AsPC-1. PSC-conditioned media (PSC-CM) induced proliferation of these cells in a dose- and time-dependent manner. Nrf2 protein was upregulated and subsequently, its transcriptional activity was increased with greater DNA binding activity and transcription of target genes. Downregulation of Nrf2 led to suppression of PSC-CM activity in BxPC-3, but not in AsPC-1 cells. However, overexpression of Nrf2 alone resulted in increased cell proliferation in both cell lines, and treatment with PSC-CM further enhanced this effect. Activation of Nrf2 pathway resulted in upregulation of metabolic genes involved in pentose phosphate pathway, glutaminolysis and glutathione biosynthesis. Downregulation and inhibition of glucose-6-phosphate-dehydrogenase with siRNA and chemical approaches reduced PSC-mediated cell proliferation. Among the cytokines present in PSC-CM, stromal-derived factor-1 alpha (SDF-1α) and interleukin-6 (IL-6) activated Nrf2 pathway to induce cell proliferation in both cells, as shown with neutralization antibodies, recombinant proteins and signaling inhibitors. Taken together, SDF-1α and IL-6 secreted from PSC induced PDAC cell proliferation via Nrf2-activated metabolic reprogramming and ROS detoxification.
    MeSH terms: Cells, Cultured; Humans; Pancreatic Neoplasms/genetics; Pancreatic Neoplasms/metabolism; Pancreatic Neoplasms/pathology; Blotting, Western; Interleukin-6/metabolism; Gene Expression Regulation, Neoplastic/drug effects; Culture Media, Conditioned/pharmacology; Reactive Oxygen Species/metabolism*; Reverse Transcriptase Polymerase Chain Reaction; Carcinoma, Pancreatic Ductal/genetics; Carcinoma, Pancreatic Ductal/metabolism; Carcinoma, Pancreatic Ductal/pathology; Cell Line, Tumor; Cell Proliferation/drug effects; Cell Proliferation/genetics*; NF-E2-Related Factor 2/genetics*; NF-E2-Related Factor 2/metabolism; Metabolic Networks and Pathways/drug effects; Metabolic Networks and Pathways/genetics; Chemokine CXCL12/metabolism; Pancreatic Stellate Cells/metabolism*; Cancer-Associated Fibroblasts/metabolism
  18. Rouffaer LO, Lens L, Haesendonck R, Teyssier A, Hudin NS, Strubbe D, et al.
    PLoS One, 2016;11(5):e0155366.
    PMID: 27168186 DOI: 10.1371/journal.pone.0155366
    In recent decades major declines in urban house sparrow (Passer domesticus) populations have been observed in north-western European cities, whereas suburban and rural house sparrow populations have remained relatively stable or are recovering from previous declines. Differential exposure to avian pathogens known to cause epidemics in house sparrows may in part explain this spatial pattern of declines. Here we investigate the potential effect of urbanization on the development of a bacterial pathogen reservoir in free-ranging house sparrows. This was achieved by comparing the prevalence of Salmonella enterica subspecies enterica serotype Typhimurium in 364 apparently healthy house sparrows captured in urban, suburban and rural regions across Flanders, Belgium between September 2013 and March 2014. In addition 12 dead birds, received from bird rescue centers, were necropsied. The apparent absence of Salmonella Typhimurium in fecal samples of healthy birds, and the identification of only one house sparrow seropositive for Salmonella spp., suggests that during the winter of 2013-2014 these birds did not represent any considerable Salmonella Typhimurium reservoir in Belgium and thus may be considered naïve hosts, susceptible to clinical infection. This susceptibility is demonstrated by the isolation of two different Salmonella Typhimurium strains from two of the deceased house sparrows: one DT99, typically associated with disease in pigeons, and one DT195, previously associated with a passerine decline. The apparent absence (prevalence: <1.3%) of a reservoir in healthy house sparrows and the association of infection with clinical disease suggests that the impact of Salmonella Typhimurium on house sparrows is largely driven by the risk of exogenous exposure to pathogenic Salmonella Typhimurium strains. However, no inference could be made on a causal relationship between Salmonella infection and the observed house sparrow population declines.
    MeSH terms: Animals; Belgium/epidemiology; Bird Diseases/microbiology; Bird Diseases/epidemiology*; Bird Diseases/transmission; Cities; Disease Reservoirs/microbiology; Female; Male; Population Dynamics; Salmonella Infections, Animal/microbiology; Salmonella Infections, Animal/epidemiology*; Salmonella Infections, Animal/transmission; Salmonella typhimurium/pathogenicity*; Salmonella typhimurium/physiology; Seasons; Urbanization; Sparrows/microbiology*
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