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Sustainable Syntheses of (−)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site
Get PDFThe jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-Targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-Tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development
Occurrence of virulent multidrug-resistant Enterococcus faecalis and Enterococcus faecium in the pigs, farmers and farm environments in Malaysia
Get PDFBackground
Enterococcus faecalis and Enterococcus faecium are ubiquitous opportunistic pathogens found in the guts of humans and farmed animals. This study aimed to determine the occurrence, antimicrobial resistance, virulence, biofilm-forming ability and genotypes of E. faecalis and E. faecium from swine farms. Correlations between the genotypes, virulotypes, antibiotic resistance, and the environmental factors such as locality of farms and farm hygiene practice were explored.
Methods
E. faecalis and E. faecium strains were isolated from the oral, rectal and fecal samples of 140 pigs; nasal, urine and fecal samples of 34 farmers working in the farms and 42 environmental samples collected from seven swine farms located in Peninsular Malaysia. Antibiotic susceptibility test was performed using the disk diffusion method, and the antibiotic resistance and virulence genes were detected by Polymerase Chain Reaction. Repetitive Extragenic Palindromic-Polymerase Chain Reaction and Pulsed-Field Gel Electrophoresis were performed to determine the clonality of the strains. Crosstab/Chi-square test and DistLM statistical analyses methods were used to determine the correlations between the genotypes, virulence factors, antibiotic resistance, and the environmental factors.
Results
A total of 211 E. faecalis and 42 E. faecium were recovered from 140 pigs, 34 farmers and 42 environmental samples collected from seven swine farms in Peninsular Malaysia. Ninety-eight percent of the strains were multidrug-resistant (resistant to chloramphenicol, tetracycline, ciprofloxacin and erythromycin). Fifty-two percent of the strains formed biofilms. Virulence genes efa, asaI, gelE, esp, cyl and ace genes were detected. Virulence genes efa and asaI were most prevalent in E. faecalis (90%) and E. faecium (43%), respectively. Cluster analyses based on REP-PCR and PFGE showed the strains were genetically diverse. Overall, the strains isolated from pigs and farmers were distinct, except for three highly similar strains found in pigs and farmers. The strains were regional- and host-specific.
Discussion
This study revealed alarming high frequencies of multidrug-resistant enterococci in pigs and swine farmers. The presence of resistance and virulence genes and the ability to form biofilm further enhance the persistence and pathogenicity of the strains. Although the overall clonality of the strains were regionals and host-specific, strains with high similarity were found in different hosts. This study reiterates a need of a more stringent regulation to ensure the proper use of antibiotics in swine husbandry to reduce the wide spread of multidrug-resistant strains
Predicting malignant progression in clinically high-risk lesions by DNA ploidy analysis and dysplasia grading
Get PDFThe value of image cytometry DNA ploidy analysis and dysplasia grading to predict malignant transformation has been determined in oral lesions considered to be at 'high' risk on the basis of clinical information and biopsy result. 10-year follow up data for 259 sequential patients with oral lesions clinically at 'high' risk of malignant transformation were matched to cancer registry and local pathology database records of malignant outcomes, ploidy result and histological dysplasia grade. In multivariate analysis (n = 228 patients), 24 developed carcinoma and of these, 14 prior biopsy samples were aneuploid. Aneuploidy was a significant predictor (hazard ratio 7.92; 95%CI 3.45, 18.17) compared with diploidy (p < 0.001). The positive predictive value (PPV) for severe dysplasia was 50% (95%CI 31.5, 68.5) and for aneuploid lesions, 33.3% (95%CI 19.0, 47.6). Combined DNA aneuploidy and severe dysplasia increased PPV to 56.3% (95% CI 31.9, 80.6). Diploid-tetraploid and non-dysplastic status had high negative predictive values (NPV) of 94.6% (95% CI 91.4, 97.8) and 99.17% (95% CI 97.4, 100.8) respectively. DNA ploidy predicts malignant transformation well and combining it with dysplasia grading gave the highest predictive value. The predictive values reported here exceed those from other investigations to date
Nerve ultrasound can distinguish chronic inflammatory demyelinating polyneuropathy from demyelinating diabetic sensorimotor polyneuropathy
No full textDiabetic patients with poor glycaemic control can demonstrate demyelinating distal sensorimotor polyneuropathy (D-DSP) on electrophysiology. Distinguishing D-DSP from chronic inflammatory demyelinating polyneuropathy (CIDP) can be challenging. In this study, we investigated the role of nerve ultrasound in differentiating the two neuropathies. Nerve ultrasound findings of D-DSP patients (fulfilling the electrophysiological but not clinical criteria for CIDP) were compared with non-diabetic CIDP patients (fulfilling both criteria). We studied 108 and 95 nerves from 9 D-DSP and 10 CIDP patients respectively. CIDP patients had significantly larger cross-sectional areas of the median nerve at the mid-arm (17.0 ± 12.5 vs 8.7 ± 2.6; p = 0.005), ulnar nerve at the wrist (7.3 ± 3.1 vs 4.1 ± 1.0; p = 0.001), mid forearm (8.8 ± 5.3 vs 5.5 ± 1.5; p = 0.002) and mid-arm (14.5 ± 14.1 vs 7.5 ± 1.9; p = 0.013), and radial nerve at mid forearm (4.1 ± 2.4 vs 1.2 ± 0.4; p < 0.001). In comparison to D-DSP, CIDP patients had markedly larger nerves at the proximal and non-entrapment sites of the upper limbs, suggesting that nerve ultrasound is useful in differentiating the two neuropathies
A high-performance control scheme for photovoltaic pumping system under sudden irradiance and load changes
No full textA low-cost photovoltaic (PV) pumping system based on three phase induction motor (IM) without the use of chemical energy storage elements is presented in this paper. The PV generator-side boost converter performs the maximum power point tracking (MPPT), while the IM−side two-level inverter regulates the net DC-link voltage and the developed electromagnetic torque by IM, which is coupled with a centrifugal pump. An improved variable step size perturb and observe (P&O) algorithm is proposed to reduce the steady-state PV power fluctuation, to accelerate the tracking operation under sudden irradiance changes, and to protect IM under load drops. The proposed algorithm is based on a current control approach of the boost converter with a model predictive current controller to select the optimal control action. Moreover, predictive torque and flux control (PTC) is used to control IM drive, due to its advantages such as faster torque response, lower torque ripple, and simplicity of implementation. Furthermore, a Takagi-Sugeno (T-S) type fuzzy logic controller (FLC) is developed in order to regulate the DC-link voltage, by producing the torque reference for PTC algorithm. In order to examine and assess the performance of the proposed control scheme for PV pumping system, a complete simulation model is developed using MATLAB/SimulinkTM environment and confirmed through real-time hardware in the loop (HIL) system. The obtained results indicate the excellent performance of the proposed control scheme, which is much better than the conventional scheme based on conventional techniques (P&O algorithm and direct torque control (DTC))
Classification, annotated list and keys for the black flies (Diptera: Simuliidae) of Peninsular Malaysia
No full textThe classification, annotated list and keys for the black fly species from Peninsular Malaysia are updated. The number of black fly species increased from 38 in 1995 to 62 (including a new species herein described) in 2018. The 62 species are classified in four subgenera of the genus Simulium: one species in Daviesellum, 35 species in Gomphostilbia, five species in Nevermannia and 21 species in Simulium. Species in the latter three subgenera are further placed in species-groups or subgroups. Keys are provided for females, males, pupae and mature larvae. Simulium (S.) perakense sp. nov. is described and placed in the S. striatum species-group. The males of S. (G.) decuplum, S. (G.) tahanense, S. (S.) malayense, the female of S. (G.) adleri, and the female and larva of S. (G.) varicorne are described for the first time. The female, male, pupa and larva of S. (G.) trangense, the male and pupa of S. (G.) varicorne and the pupa of S. (G.) adleri are redescribed. Simulium(G.) sp. A is identified as S. (G.) pegalanense. Brief notes for each species are given on morphological characteristics, aquatic habitats and geographical distributions
A new black fly species of Simulium (Simulium) (Diptera: Simuliidae) from Taiwan
No full textA new black fly species, Simulium taichungense, is described on the basis of one female, one male and two pupal exuviae from Taiwan. This new species is placed in the S. crocinum species-group of Simulium (Simulium) (Diptera: Simuliidae). It is characterized by the pupal gill with six unpigmented short filaments and pupal abdomen with distinct spine-combs on the dorsal surface of segments 7-9, by which it is easily distinguished from most species in the S. crocinum speciesgroup including two species from Taiwan: Simulium serenum Huang & Takaoka and S. ufengense Takaoka. It is the third species of the S. crocinum species-group from Taiwan. In addition, the male of S. serenum is described for the first time, and intraspecific variations in a few features of the male of S. chungi Takaoka & Huang of the S. chungi species-group are noted
Environmental forensic techniques in identifying the sources of 16 USEPA priority pollutants Polycyclic Aromatic Hydrocarbons (PAHs) at the Langat River, Selangor, Malaysia
No full textTwenty-two surface sediment samples were collected from the Langat River, Selangor, Malaysia in January 2010. The concentration of 16 USEPA priority PAHs were determined and quantified by gas chromatography coupled with mass spectrometry detector (GC-MS). The 16 PAHs concentration ranged from 37.91 to 299.68 ng/g dry weight and are within low to moderate pollution range. Cluster analysis showed that SL08, SL09, SL10, SL15 and SL22 can be discriminated as having high pollution loading PAHs due to industrialized region and shipping boat traffic. In this work, Principal Component Analysis (PCA) and PCA association with Multiple Linear Regressions (PCA-MLR) to identify and apportion possible sources of PAHs. Three sources of PAHs were identified: (1) traffic emission (91.57%); (2) coal or wood combustion (6.63%); and (3) spillage of petroleum based products (1.80%). Langat River is highly contaminated by PAHs from pyrogenic sources, in particular 4 rings PAHs (28.87-79.52%) and 5 to 6 rings PAHs (2.69-57.44%)
CloudProcMon: A Non-Intrusive Cloud Monitoring Framework
No full textCloud computing has seen massive growth in this decade. With the rapid development of cloud networks, cloud monitoring has become essential for running cloud systems smoothly. Cloud monitoring collects monitoring metrics from the cloud's physical and virtual infrastructures. In terms of data collection, cloud monitoring can be intrusive or non-intrusive. Monitoring data collection non-intrusively from the host operating system (OS) is a challenging task. The aim of this paper was to collect monitoring data from the host OS non-intrusively and to link those data with the cloud controller for use in monitoring. Monitoring data were collected from Procfs of the host OS and that information was linked with the monitoring dashboard on the cloud controller node. The results show that the proposed solution is an efficient, lightweight, and scalable cloud monitoring framework that produces negligible overhead