Browse publications by year: 2014

Fulltext Epidemiology of intestinal polyparasitism among Orang Asli school children in rural Malaysia

Al-Delaimy AK, Al-Mekhlafi HM, Nasr NA, Sady H, Atroosh WM, Nashiry M, et al.

PLoS Negl Trop Dis, 2014 Aug;8(8):e3074.
PMID: 25144662 DOI: 10.1371/journal.pntd.0003074

This cross-sectional study aimed to investigate the current prevalence and risk factors associated with intestinal polyparasitism (the concurrent infection with multiple intestinal parasite species) among Orang Asli school children in the Lipis district of Pahang state, Malaysia.

MeSH terms: Age Factors; Animals; Child; Cross-Sectional Studies; Feces/parasitology; Female; Humans; Hygiene; Intestinal Diseases, Parasitic/etiology; Intestinal Diseases, Parasitic/epidemiology*; Malaysia/epidemiology; Male; Risk Factors; Prevalence
Fulltext Is Matang Mangrove Forest in Malaysia sustainably rejuvenating after more than a century of conservation and harvesting management?

Goessens A, Satyanarayana B, Van der Stocken T, Quispe Zuniga M, Mohd-Lokman H, Sulong I, et al.

PLoS One, 2014;9(8):e105069.
PMID: 25144689 DOI: 10.1371/journal.pone.0105069

Matang Mangrove Forest Reserve (MMFR) in Peninsular Malaysia is under systematic management since 1902 and still considered as the best managed mangrove forest in the world. The present study on silvimetrics assessed the ongoing MMFR forest management, which includes a first thinning after 15 years, a second thinning after 20 years and clear-felling of 30-year old forest blocks, for its efficiency and productivity in comparison to natural mangroves. The estimated tree structural parameters (e.g. density, frequency) from three different-aged mangrove blocks of fifteen (MF15), twenty (MF20), and thirty (MF30) years old indicated that Bruguiera and Excoecaria spp. did not constitute a significant proportion of the vegetation (<5%), and hence the results focused majorly on Rhizophora apiculata. The density of R. apiculata at MF15, MF20 and MF30 was 4,331, 2,753 and 1,767 stems ha(-1), respectively. In relation to ongoing practices of the artificial thinnings at MMFR, the present study suggests that the first thinning could be made earlier to limit the loss of exploitable wood due to natural thinning. In fact, the initial density at MF15 was expected to drop down from 6,726 to 1,858 trees ha(-1) before the first thinning. Therefore the trees likely to qualify for natural thinning, though having a smaller stem diameter, should be exploited for domestic/commercial purposes at an earlier stage. The clear-felling block (MF30) with a maximum stem diameter of 30 cm was estimated to yield 372 t ha(-1) of the above-ground biomass and suggests that the mangrove management based on a 30-year rotation is appropriate for the MMFR. Since Matang is the only iconic site that practicing sustainable wood production, it could be an exemplary to other mangrove locations for their improved management.

MeSH terms: Conservation of Natural Resources*; Malaysia; Forests*
LPXRFa, the piscine ortholog of GnIH, and LPXRF receptor positively regulate gonadotropin secretion in Tilapia (Oreochromis niloticus)

Biran J, Golan M, Mizrahi N, Ogawa S, Parhar IS, Levavi-Sivan B

Endocrinology, 2014 Nov;155(11):4391-401.
PMID: 25144920 DOI: 10.1210/en.2013-2047

LPXRFamide (LPXRFa) peptides have been characterized for their ability to inhibit gonadotropin (GTH) release in birds and stimulate growth hormone (GH) release in frogs. However, their involvement in regulating the reproductive hypothalamo-pituitary-gonadal axis in mammals and fish is inconclusive. To study the role of LPXRFa peptides in the regulation of GTH secretion, we cloned tilapia LPXRFa and LPXRF receptor (LPXRF-R). Processing of the tilapia preproLPXRFa liberated three mature LPXRFa peptides that varied in size and post-translational modifications. Phylogenetic analysis of LPXRFa and the closely related RFamide peptide PQRFa showed clear clustering of each peptide sequence with its orthologs from various vertebrates. Signal-transduction analysis of the tilapia LPXRF-R in COS-7 cells showed clear stimulation of CRE-dependent luciferase activity, whereas the human NPFFR1 showed suppression of forskolin-induced CRE-dependent activity in this system. Administration of the tilapia pyroglutaminated LPXRFa-2 peptide to primary cell culture of tilapia pituitaries, or to reproductive female tilapia by ip injection, positively regulated both LH and FSH release in vivo and in vitro. Using double-labeled fluorescent in-situ hybridization and immunofluorescence, βLH cells were found to co-express both tilapia lpxrf and tilapia lpxrf-r mRNA, whereas some of the βFSH cells coexpressed only lpxrf-r mRNA. No coexpression of tilapia lpxrf-r was identified in GH-positive cells. These findings suggest that the LPXRFa system is a potent positive regulator of the reproductive neuroendocrine axis of tilapia.

MeSH terms: Amino Acid Sequence; Animals; Cells, Cultured; Cercopithecus aethiops; Cloning, Molecular; Female; Gonadotropins/secretion*; Humans; Male; Molecular Sequence Data; Neuropeptides/pharmacology; Neuropeptides/physiology*; Phylogeny; Sequence Homology; Receptors, Neuropeptide/physiology*; COS Cells; Cichlids/genetics*; Cichlids/metabolism*
Fulltext The use of protein-DNA, chromatin immunoprecipitation, and transcriptome arrays to describe transcriptional circuits in the dehydrated male rat hypothalamus

Qiu J, Kleineidam A, Gouraud S, Yao ST, Greenwood M, Hoe SZ, et al.

Endocrinology, 2014 Nov;155(11):4380-90.
PMID: 25144923 DOI: 10.1210/en.2014-1448

The supraoptic nucleus (SON) of the hypothalamus is responsible for maintaining osmotic stability in mammals through its elaboration of the antidiuretic hormone arginine vasopressin. Upon dehydration, the SON undergoes a function-related plasticity, which includes remodeling of morphology, electrical properties, and biosynthetic activity. This process occurs alongside alterations in steady state transcript levels, which might be mediated by changes in the activity of transcription factors. In order to identify which transcription factors might be involved in changing patterns of gene expression, an Affymetrix protein-DNA array analysis was carried out. Nuclear extracts of SON from dehydrated and control male rats were analyzed for binding to the 345 consensus DNA transcription factor binding sequences of the array. Statistical analysis revealed significant changes in binding to 26 consensus elements, of which EMSA confirmed increased binding to signal transducer and activator of transcription (Stat) 1/Stat3, cellular Myelocytomatosis virus-like cellular proto-oncogene (c-Myc)-Myc-associated factor X (Max), and pre-B cell leukemia transcription factor 1 sequences after dehydration. Focusing on c-Myc and Max, we used quantitative PCR to confirm previous transcriptomic analysis that had suggested an increase in c-Myc, but not Max, mRNA levels in the SON after dehydration, and we demonstrated c-Myc- and Max-like immunoreactivities in SON arginine vasopressin-expressing cells. Finally, by comparing new data obtained from Roche-NimbleGen chromatin immunoprecipitation arrays with previously published transcriptomic data, we have identified putative c-Myc target genes whose expression changes in the SON after dehydration. These include known c-Myc targets, such as the Slc7a5 gene, which encodes the L-type amino acid transporter 1, ribosomal protein L24, histone deactylase 2, and the Rat sarcoma proto-oncogene (Ras)-related nuclear GTPase.

MeSH terms: Animals; Dehydration/genetics*; Dehydration/metabolism; DNA/metabolism; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Hypothalamus/metabolism*; Hypothalamus/chemistry; Male; Promoter Regions, Genetic; Transcription Factors/metabolism; Rats, Sprague-Dawley; Gene Expression Profiling*; Microarray Analysis/methods*; Chromatin Immunoprecipitation*; Rats; Gene Regulatory Networks*; Transcriptome
Thermoluminescence characteristics of Nd-doped SiO2 optical fibers irradiated with the (60)Co gamma rays

Refaei A, Wagiran H, Saeed MA, Hosssain I

Appl Radiat Isot, 2014 Dec;94:89-92.
PMID: 25146569 DOI: 10.1016/j.apradiso.2014.07.012

Thermoluminescence (TL) properties (radiation sensitivity, dose response, signal fading) of Nd-doped SiO2 optical fibers irradiated with 1.25MeV photons to 1-50Gy were studied. The peak of the glow curve is around 190°C regardless of the dose. The dose response is linear up to 50Gy. The radiation sensitivity is 219nCmg(-1)Gy(-1). The fiber can be a potential candidate for photon radiotherapy dosimetry due to its high radiation sensitivity, linear dose response in a wide range, slow fading, and high spatial resolution due to the small size of the fiber.

MeSH terms: Dietary Fiber; Radiation Tolerance; Radiometry; Silicon Dioxide; Thermoluminescent Dosimetry; Photons; Laxatives; Optical Fibers
Fulltext Repeated batch fermentation biotechnology for the biosynthesis of lipid and gamma-linolenic acid by Cunninghamella bainieri 2A1

Ganjali Dashti M, Abdeshahian P, Wan Yusoff WM, Kalil MS, Abdul Hamid A

Biomed Res Int, 2014;2014:831783.
PMID: 25147817 DOI: 10.1155/2014/831783

The biosynthesis of biomedical products including lipid and gamma-linolenic acid (GLA) by Cunninghamella bainieri 2A1 was studied in repeated batch fermentation. Three key process variables, namely, glucose concentration, ammonium tartrate concentration, and harvesting time, were optimized using response surface methodology. Repeated batch fermentation was carried out by the cultivation of Cunninghamella bainieri 2A1 in nitrogen-limited medium with various nitrogen concentration (1-4 g/L) and glucose concentration (20-40 g/L) at three time intervals (12 h, 24 h, and 48 h). Experimental results showed that the highest lipid concentration of 6.2 g/L and the highest GLA concentration of 0.4 g/L were obtained in optimum conditions, where 20.2 g/L glucose, 2.12 g/L ammonium tartrate, and 48 h harvesting time were utilized. Statistical results showed that the interaction between glucose and ammonium tartrate concentration had highly significant effects on lipid and GLA biosynthesis (P < 0.01). Moreover, harvesting time had a significant interaction effect with glucose and ammonium tartrate concentration on lipid production (P < 0.05).

MeSH terms: Biotechnology/methods; Culture Media; Fermentation/physiology*; Glucose/metabolism; Lipids/biosynthesis*; Nitrogen/metabolism; Tartrates/metabolism; gamma-Linolenic Acid/biosynthesis*; gamma-Linolenic Acid/metabolism; Bioreactors/microbiology; Cunninghamella/metabolism*
Fulltext Apoptosis-inducing effect of three medicinal plants on oral cancer cells KB and ORL-48

Majid MZ, Zaini ZM, Razak FA

ScientificWorldJournal, 2014;2014:125353.
PMID: 25147833 DOI: 10.1155/2014/125353

Brucea javanica, Azadirachta indica, and Typhonium flagelliforme are medicinal plants commonly used to treat conditions associated with tumour formation. This study aimed to determine the antiproliferative activity of these plants extracts on KB and ORL-48 oral cancer cell lines and to suggest their mode of cell death. The concentration producing 50% cell inhibition (IC50) was determined and the activity was examined under an inverted microscope. Immunohistochemistry fluorescent staining method (TUNEL) was performed to indicate the mechanism of cell death and the fragmented DNA band pattern produced was obtained for verification. Compared to Azadirachta sp. and Typhonium sp., the antiproliferative activity of Brucea sp. extract was the most potent on both KB and ORL-48 cells with IC50 of 24.37 ± 1.75 and 6.67 ± 1.15 µg/mL, respectively. Signs of cell attrition were observed 24 hr after treatment. Green fluorescent spots indicating cell death by apoptosis were observed in images of both cells following treatment with all the three extracts. DNA fragments harvested from Brucea-treated cells produced bands in a ladder pattern suggesting the apoptotic effect of the extract. It is thus concluded that Brucea sp. extract exhibited cytotoxic activity on ORL-48 cells and their action mechanism is via apoptosis.

MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology*; Antineoplastic Agents, Phytogenic/chemistry; Humans; Mouth Neoplasms/metabolism; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Plants, Medicinal/chemistry*; Apoptosis/drug effects*; Inhibitory Concentration 50; Cell Line, Tumor; Cell Proliferation/drug effects; DNA Fragmentation/drug effects
Fulltext Effects of nonsurgical periodontal therapy on clinical response, microbiological profile, and glycemic control in Malaysian subjects with type 1 diabetes

Buzinin SM, Alabsi AM, Tan AT, Vincent-Chong VK, Swaminathan D

ScientificWorldJournal, 2014;2014:232535.
PMID: 25147841 DOI: 10.1155/2014/232535

The association between diabetes mellitus and chronic periodontal disease has long been established. Most of the researches linking these two very common chronic diseases were based on type 2 diabetes mellitus and chronic periodontal disease. However, this study was conducted to investigate the association between type 1 diabetes and chronic periodontal disease in Malaysian subjects. Forty-one Malaysian subjects, of which 20 subjects were type 1 diabetics and with chronic periodontal disease (test group) and 21 subjects with only chronic periodontal disease (control group), were included in the study. Periodontal parameters and plaque samples for microbiological evaluation were done at baseline, 2 and 3 months after nonsurgical periodontal therapy. Blood samples were taken from only the test group and evaluated for HbA1c at baseline and 3 months after periodontal therapy. There were no statistically significant difference in periodontal parameters between groups (P>0.05) and no significant improvement in the level of HbA1c in the test group. Microbiological studies indicated that there were significant reductions in the levels of the tested pathogens in both groups. The results of our study were similar to the findings of several other studies that had been done previously.

MeSH terms: Adult; Blood Glucose*; Chronic Disease; Diabetes Mellitus, Type 1/complications; Diabetes Mellitus, Type 1/drug therapy; Diabetes Mellitus, Type 1/metabolism*; Diabetes Mellitus, Type 1/microbiology*; Female; Hemoglobin A, Glycosylated/metabolism; Humans; Hypoglycemic Agents/therapeutic use; Malaysia; Male; Middle Aged; Periodontal Diseases/complications*; Periodontal Diseases/diagnosis; Periodontal Diseases/therapy*; Periodontium/microbiology; Treatment Outcome; Microbiota*
Fulltext Effect of codon optimisation on the production of recombinant fish growth hormone in Pichia pastoris

Rothan HA, Huy TS, Mohamed Z

ScientificWorldJournal, 2014;2014:514835.
PMID: 25147851 DOI: 10.1155/2014/514835

This study was established to test the hypothesis of whether the codon optimization of fish growth hormone gene (FGH) based on P. pastoris preferred codon will improve the quantity of secreted rFGH in culture supernatant that can directly be used as fish feed supplements. The optimized FGH coding sequence (oFGH) and native sequence (nFGH) of giant grouper fish (Epinephelus lanceolatus) were cloned into P. pastoris expression vector (pPICZαA) downstream of alcohol oxidase gene (AOX1) for efficient induction of extracellular rFGH by adding 1% of absolute methanol. The results showed that recombinant P. pastoris was able to produce 2.80 ± 0.27 mg of oFGH compared to 1.75 ± 0.25 of nFGH in one litre of culture supernatant. The total body weight of tiger grouper fingerlings fed with oFGH increased significantly at third (P < 0.05) and fourth weeks (P < 0.01) of four-week experiment period compared to those fed with nFGH. Both oFGH and nFGH significantly enhanced the final biomass and fish survival percentage. In conclusion, codon optimization of FGH fragment was useful to increase rFGH quantity in the culture supernatant of P. pastoris that can be directly used as fish feed supplements. Further studies are still required for large scale production of rFGH and practical application in aquaculture production.

MeSH terms: Animals; Base Sequence; Cloning, Molecular; Codon*; Fishes/genetics*; Fishes/metabolism; Molecular Sequence Data; Pichia/genetics*; Pichia/metabolism; Recombinant Proteins*; Growth Hormone/biosynthesis*; Growth Hormone/genetics*; Gene Expression; Sequence Analysis, DNA
Fulltext Optimization of reflux conditions for total flavonoid and total phenolic extraction and enhanced antioxidant capacity in Pandan (Pandanus amaryllifolius Roxb.) using response surface methodology

Ghasemzadeh A, Jaafar HZ

ScientificWorldJournal, 2014;2014:523120.
PMID: 25147852 DOI: 10.1155/2014/523120

Response surface methodology was applied to optimization of the conditions for reflux extraction of Pandan (Pandanus amaryllifolius Roxb.) in order to achieve a high content of total flavonoids (TF), total phenolics (TP), and high antioxidant capacity (AC) in the extracts. Central composite experimental design with three factors and three levels was employed to consider the effects of the operation parameters, including the methanol concentration (MC, 40%-80%), extraction temperature (ET, 40-70°C), and liquid-to-solid ratio (LS ratio, 20-40 mL/g) on the properties of the extracts. Response surface plots showed that increasing these operation parameters induced the responses significantly. The TF content and AC could be maximized when the extraction conditions (MC, ET, and LS ratio) were 78.8%, 69.5°C, and 32.4 mL/g, respectively, whereas the TP content was optimal when these variables were 75.1%, 70°C, and 31.8 mL/g, respectively. Under these optimum conditions, the experimental TF and TP content and AC were 1.78, 6.601 mg/g DW, and 87.38%, respectively. The optimized model was validated by a comparison of the predicted and experimental values. The experimental values were found to be in agreement with the predicted values, indicating the suitability of the model for optimizing the conditions for the reflux extraction of Pandan.

MeSH terms: Antioxidants/pharmacology; Antioxidants/chemistry*; Flavonoids/chemistry*; Phenols/chemistry*; Plant Extracts/pharmacology; Plant Extracts/chemistry*; Pandanaceae/chemistry*; Phytochemicals/pharmacology; Phytochemicals/chemistry
Fulltext Wide distribution of virulence genes among Enterococcus faecium and Enterococcus faecalis clinical isolates

Soheili S, Ghafourian S, Sekawi Z, Neela V, Sadeghifard N, Ramli R, et al.

ScientificWorldJournal, 2014;2014:623174.
PMID: 25147855 DOI: 10.1155/2014/623174

Enterococcus, a Gram-positive facultative anaerobic cocci belonging to the lactic acid bacteria of the phylum Firmicutes, is known to be able to resist a wide range of hostile conditions such as different pH levels, high concentration of NaCl (6.5%), and the extended temperatures between 5(°)C and 65(°)C. Despite being the third most common nosocomial pathogen, our understanding on its virulence factors is still poorly understood. The current study was aimed to determine the prevalence of different virulence genes in Enterococcus faecalis and Enterococcus faecium. For this purpose, 79 clinical isolates of Malaysian enterococci were evaluated for the presence of virulence genes. pilB, fms8, efaAfm, and sgrA genes are prevalent in all clinical isolates. In conclusion, the pathogenicity of E. faecalis and E. faecium could be associated with different virulence factors and these genes are widely distributed among the enterococcal species.

MeSH terms: Genes, Bacterial; Humans; Enterococcus faecalis/genetics*; Enterococcus faecalis/isolation & purification; Enterococcus faecalis/pathogenicity; Virulence; Gram-Positive Bacterial Infections/microbiology*; Enterococcus faecium/genetics*; Enterococcus faecium/isolation & purification; Enterococcus faecium/pathogenicity; Virulence Factors/genetics*
Fulltext A novel approach for blast-induced flyrock prediction based on imperialist competitive algorithm and artificial neural network

Marto A, Hajihassani M, Armaghani DJ, Mohamad ET, Makhtar AM

ScientificWorldJournal, 2014;2014:643715.
PMID: 25147856 DOI: 10.1155/2014/643715

Flyrock is one of the major disturbances induced by blasting which may cause severe damage to nearby structures. This phenomenon has to be precisely predicted and subsequently controlled through the changing in the blast design to minimize potential risk of blasting. The scope of this study is to predict flyrock induced by blasting through a novel approach based on the combination of imperialist competitive algorithm (ICA) and artificial neural network (ANN). For this purpose, the parameters of 113 blasting operations were accurately recorded and flyrock distances were measured for each operation. By applying the sensitivity analysis, maximum charge per delay and powder factor were determined as the most influential parameters on flyrock. In the light of this analysis, two new empirical predictors were developed to predict flyrock distance. For a comparison purpose, a predeveloped backpropagation (BP) ANN was developed and the results were compared with those of the proposed ICA-ANN model and empirical predictors. The results clearly showed the superiority of the proposed ICA-ANN model in comparison with the proposed BP-ANN model and empirical approaches.

MeSH terms: Algorithms*; Neural Networks (Computer)*
Fulltext Null steering of adaptive beamforming using linear constraint minimum variance assisted by particle swarm optimization, dynamic mutated artificial immune system, and gravitational search algorithm

Darzi S, Kiong TS, Islam MT, Ismail M, Kibria S, Salem B

ScientificWorldJournal, 2014;2014:724639.
PMID: 25147859 DOI: 10.1155/2014/724639

Linear constraint minimum variance (LCMV) is one of the adaptive beamforming techniques that is commonly applied to cancel interfering signals and steer or produce a strong beam to the desired signal through its computed weight vectors. However, weights computed by LCMV usually are not able to form the radiation beam towards the target user precisely and not good enough to reduce the interference by placing null at the interference sources. It is difficult to improve and optimize the LCMV beamforming technique through conventional empirical approach. To provide a solution to this problem, artificial intelligence (AI) technique is explored in order to enhance the LCMV beamforming ability. In this paper, particle swarm optimization (PSO), dynamic mutated artificial immune system (DM-AIS), and gravitational search algorithm (GSA) are incorporated into the existing LCMV technique in order to improve the weights of LCMV. The simulation result demonstrates that received signal to interference and noise ratio (SINR) of target user can be significantly improved by the integration of PSO, DM-AIS, and GSA in LCMV through the suppression of interference in undesired direction. Furthermore, the proposed GSA can be applied as a more effective technique in LCMV beamforming optimization as compared to the PSO technique. The algorithms were implemented using Matlab program.

MeSH terms: Algorithms*; Models, Theoretical*
Fulltext Stimulatory effects of gamma irradiation on phytochemical properties, mitotic behaviour, and nutritional composition of sainfoin (Onobrychis viciifolia Scop.)

Mohajer S, Taha RM, Lay MM, Esmaeili AK, Khalili M

ScientificWorldJournal, 2014;2014:854093.
PMID: 25147870 DOI: 10.1155/2014/854093

Sainfoin (Onobrychis viciifolia Scop. Syn. Onobrychis sativa L.) is a bloat-safe forage crop with high levels of tannins, which is renowned for its medicinal qualities in grazing animals. Mutagenesis technique was applied to investigate the influence of gamma irradiation at 30, 60, 90, and 120 Gy on mitotic behavior, in vitro growth factors, phytochemical and nutritional constituents of sainfoin. Although a percentage of plant necrosis and non-growing seed were enhanced by irradiation increment, the germination speed was significantly decreased. It was observed that gamma irradiated seeds had higher value of crude protein and dry matter digestibility compared to control seeds. Toxicity of copper was reduced in sainfoin irradiated seeds at different doses of gamma rays. Anthocyanin content also decreased in inverse proportion to irradiation intensity. Accumulation of phenolic and flavonoid compounds was enhanced by gamma irradiation exposure in leaf cells. HPLC profiles differed in peak areas of the two important alkaloids, Berberine and Sanguinarine, in 120 Gy irradiated seeds compared to control seeds. There were positive correlations between irradiation dose and some abnormality divisions such as laggard chromosome, micronucleus, binucleated cells, chromosome bridge, and cytomixis. In reality, radiocytological evaluation was proven to be essential in deducing the effectiveness of gamma irradiation to induce somaclonal variation in sainfoin.

MeSH terms: Gamma Rays*; Fabaceae/physiology*; Fabaceae/radiation effects*; Mitosis/radiation effects*; Seeds/physiology; Seeds/radiation effects; Quantitative Trait, Heritable; Phytochemicals/chemistry*
Fulltext Factors that are associated with the risk of acquiring Plasmodium knowlesi malaria in Sabah, Malaysia: a case-control study protocol

Grigg MJ, William T, Drakeley CJ, Jelip J, von Seidlein L, Barber BE, et al.

BMJ Open, 2014 Aug 22;4(8):e006004.
PMID: 25149186 DOI: 10.1136/bmjopen-2014-006004

INTRODUCTION: Plasmodium knowlesi has long been present in Malaysia, and is now an emerging cause of zoonotic human malaria. Cases have been confirmed throughout South-East Asia where the ranges of its natural macaque hosts and Anopheles leucosphyrus group vectors overlap. The majority of cases are from Eastern Malaysia, with increasing total public health notifications despite a concurrent reduction in Plasmodium falciparum and P. vivax malaria. The public health implications are concerning given P. knowlesi has the highest risk of severe and fatal disease of all Plasmodium spp in Malaysia. Current patterns of risk and disease vary based on vector type and competence, with individual exposure risks related to forest and forest-edge activities still poorly defined. Clustering of cases has not yet been systematically evaluated despite reports of peri-domestic transmission and known vector competence for human-to-human transmission.
METHODS AND ANALYSIS: A population-based case-control study will be conducted over a 2-year period at two adjacent districts in north-west Sabah, Malaysia. Confirmed malaria cases presenting to the district hospital sites meeting relevant inclusion criteria will be requested to enrol. Three community controls matched to the same village as the case will be selected randomly. Study procedures will include blood sampling and administration of household and individual questionnaires to evaluate potential exposure risks associated with acquisition of P. knowlesi malaria. Secondary outcomes will include differences in exposure variables between P. knowlesi and other Plasmodium spp, risk of severe P. knowlesi malaria, and evaluation of P. knowlesi case clustering. Primary analysis will be per protocol, with adjusted ORs for exposure risks between cases and controls calculated using conditional multiple logistic regression models.
ETHICS: This study has been approved by the human research ethics committees of Malaysia, the Menzies School of Health Research, Australia, and the London School of Hygiene and Tropical Medicine, UK.

MeSH terms: Animals; Anopheles; Disease Vectors*; Female; Humans; Macaca; Malaria/etiology; Malaria/parasitology; Malaria/transmission*; Malaysia; Male; Research Design; Residence Characteristics; Risk Factors; Case-Control Studies; Malaria, Falciparum; Malaria, Vivax; Plasmodium knowlesi*; Forests
Rational design of carbonitrile-carboxaldehyde cation receptor models: probing the nature of the heteroatom-metal interaction

Rosli AN, Abu Bakar MA, Lee VS, Zain SM, Ahmad MR, Abdul Manan NS, et al.

J Mol Model, 2014 Sep;20(9):2428.
PMID: 25149440 DOI: 10.1007/s00894-014-2428-9

In this work, hybrid functional and G4 methods were employed in the rational design of carbonitrile-carboxaldehyde receptor models for cation recognition. Electron-sharing and ionic interactions between the models and the cations were analyzed utilizing the concepts of overlap population, atomic valence, electrostatic potential, and CHELPG charge in order to elucidate the nature of the heteroatom-metal interaction, the N versus O disparity, and the effect of pH. Receptor fragment models from ionomycin were employed to rationalize the selection of receptor models for discriminating group I cations and enhancing the selectivity for Mg(II) rather than Ca(II), and to examine the effects of keto-enol forms and negatively charged sites. The changes in geometries, overlap population, metal valence, and CHELPG charge upon solvation in heptane medium as compared to the gas phase were negligible. The optimized geometries reveal that the interaction between group II cations and the keto, enol, and enolate forms of 2-cyanoethanal causes 12 % bending of the C-C-N angle from linearity. Overlap populations show that the electron-sharing interaction favors group II cations but that the same mechanism allows Li(I) to compete. The total spin of Li(I) is 17 % greater than that of Ca(II), but the G4 binding energies of the two are separated by more than 50 kcal/mol, favoring group II cations, which may eliminate interference from Li(I). 1,2-Dicyanoethylene, which has only one form, shows similar characteristics. CHELPG analysis shows that Mg(II) transfers 25 and 18 % of its positive charge to 2-cyanoethanal enolate and 1,2-dicyanoethylene, respectively. Hydrogen atoms receive most of the positive charge in both receptors, but the N-termini exhibit strikingly different characteristics. Electrostatic potential contour profiles were found to be in good agreement with the atomic charge distributions. The application of uncharged 1,3-dicarbonyl and 2-cyanocarbonyl receptors and a judicious choice of polymeric membrane that suppresses the Hofmeister effect should lead to high selectivity for magnesium, whereas the utilization of multiple negatively charged ionophores should result in selectivity for calcium.
Overexpression, purification and validation of antigenic Salmonella enterica serovar Typhi proteins identified from LC-MS/MS

Chin CF, Teh BA, Anthony AA, Aziah I, Ismail A, Ong EB, et al.

Appl Biochem Biotechnol, 2014 Nov;174(5):1897-906.
PMID: 25149461 DOI: 10.1007/s12010-014-1173-y

In our earlier study, an immunoblot analysis using sera from febrile patients revealed that a 50-kDa band from an outer membrane protein fraction of Salmonella enterica serovar Typhi was specifically recognized only by typhoid sera and not sera from other febrile illnesses. Here, we investigated the identities of the proteins contained in the immunogenic 50-kDa band to pinpoint antigens responsible for its immunogenicity. We first used LC-MS/MS for protein identification, then used the online tool ANTIGENpro for antigenicity prediction and produced recombinant proteins of the lead antigens for validation in an enzyme-linked immunosorbent assay (ELISA). We found that proteins TolC, GlpK and SucB were specific to typhoid sera but react to antibodies differently under native and denatured conditions. This difference suggests the presence of linear and conformational epitopes on these proteins.

MeSH terms: Epitopes/immunology*; Epitopes/chemistry*; Bacterial Outer Membrane Proteins/immunology*; Bacterial Outer Membrane Proteins/isolation & purification; Bacterial Outer Membrane Proteins/chemistry*; Chromatography, Liquid; Humans; Salmonella typhi/immunology*; Salmonella typhi/chemistry*; Mass Spectrometry; Typhoid Fever/immunology*; Typhoid Fever/microbiology; Immunoblotting; Up-Regulation; Epitope Mapping
Transcriptional profiling of the oesophageal gland region of male worms of Schistosoma mansoni

Nawaratna SS, Gobert GN, Willis C, Chuah C, McManus DP, Jones MK

Mol Biochem Parasitol, 2014 Sep;196(2):82-9.
PMID: 25149559 DOI: 10.1016/j.molbiopara.2014.08.002

The intestinal tract of schistosomes opens at the mouth and leads into the foregut or oesophageal region that is lined with syncytium continuous with the apical cytoplasm of the tegument. The oesophagus is surrounded by a specialised gland, the oesophageal gland. This gland releases materials into the lumen of the oesophagus and the region is thought to initiate the lysis of erythrocytes and neutralisation of immune effectors of the host. The oesophageal region is present in the early invasive schistosomulum, a stage potentially targetable by anti-schistosome vaccines. We used a 44k oligonucleotide microarray to identify highly up-regulated genes in microdissected frozen sections of the oesophageal gland of male worms of S. mansoni. We show that 122 genes were up-regulated 2-fold or higher in the oesophageal gland compared with a whole male worm tissue control. The enriched genes included several associated with lipid metabolism and transmembrane transport as well as some micro-exon genes. Since the oesophageal gland is important in the initiation of digestion and the fact that it develops early after invasion of the mammalian host, further study of selected highly up-regulated functionally important genes in this tissue may reveal new anti-schistosome intervention targets for schistosomiasis control.

MeSH terms: Animals; Male; Molecular Sequence Data; Schistosoma mansoni/genetics*; Schistosoma mansoni/metabolism; Schistosomiasis mansoni/parasitology*; Helminth Proteins/genetics*; Helminth Proteins/metabolism; Oligonucleotide Array Sequence Analysis; Gene Expression Profiling*
Geometric variable designs of cam/post mechanisms influence the kinematics of knee implants

Fallahiarezoodar A, Abdul Kadir MR, Alizadeh M, Naveen SV, Kamarul T

Knee Surg Sports Traumatol Arthrosc, 2014 Dec;22(12):3019-27.
PMID: 25149643 DOI: 10.1007/s00167-014-3227-7

PURPOSE: Reproducing the femoral rollback through specially designed mechanism in knee implants is required to achieve full knee function in total knee arthroplasty. Most contemporary implants use cam/post mechanism to replace the function of Posterior Cruciate Ligament. This study was aimed to determine the most appropriate cam and post designs to produce normal femoral rollback of the knee.
METHODS: Three different cams (triangle, ellipse, and circle) and three different posts (straight, convex, concave) geometries were considered in this study and were analysed using kinematic analyses. Femoral rollback did not occur until reaching 50° of knee flexion. Beyond this angle, two of the nine combinations demonstrate poor knee flexion and were eliminated from the study.
RESULTS: The combination of circle cam with concave post, straight post and convex post showed 15.6, 15.9 and 16.1 mm posterior translation of the femur, respectively. The use of ellipse cam with convex post and straight post demonstrated a 15.3 and 14.9 mm femoral rollback, whilst the combination of triangle cam with convex post and straight post showed 16.1 and 15.8 mm femoral rollback, respectively.
CONCLUSION: The present study demonstrates that the use of circle cam and convex post created the best femoral rollback effect which in turn produces the highest amount of knee flexion. The findings of the study suggest that if the design is applied for knee implants, superior knee flexion may be possible for future patients.
LEVEL OF EVIDENCE: IV.

MeSH terms: Aged; Aged, 80 and over; Biomechanical Phenomena; Computer Simulation; Female; Femur/physiopathology; Femur/surgery*; Humans; Knee Joint/physiopathology; Knee Joint/surgery*; Knee Prosthesis*; Male; Prosthesis Design*; Tibia/physiopathology; Tibia/surgery; Range of Motion, Articular; Arthroplasty, Replacement, Knee/instrumentation*; Imaging, Three-Dimensional
Fulltext FusoBase: an online Fusobacterium comparative genomic analysis platform

Ang MY, Heydari H, Jakubovics NS, Mahmud MI, Dutta A, Wee WY, et al.

Database (Oxford), 2014;2014.
PMID: 25149689 DOI: 10.1093/database/bau082

Fusobacterium are anaerobic gram-negative bacteria that have been associated with a wide spectrum of human infections and diseases. As the biology of Fusobacterium is still not well understood, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of infections and diseases. To facilitate the ongoing genomic research on Fusobacterium, a specialized database with easy-to-use analysis tools is necessary. Here we present FusoBase, an online database providing access to genome-wide annotated sequences of Fusobacterium strains as well as bioinformatics tools, to support the expanding scientific community. Using our custom-developed Pairwise Genome Comparison tool, we demonstrate how differences between two user-defined genomes and how insertion of putative prophages can be identified. In addition, Pathogenomics Profiling Tool is capable of clustering predicted genes across Fusobacterium strains and visualizing the results in the form of a heat map with dendrogram.

MeSH terms: Fusobacterium*; Software; User-Computer Interface; Cluster Analysis; Genome, Bacterial*; Internet*; Genomics/methods*; Databases, Genetic*

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