P‐21POSITIVE PREDICTIVE VALUE OF CERVICAL SMEARS REPORTED AS MILD DYSKARYOSIS

Objective: Recent national guidelines (NHSCSP Document 20) recommend the referral of patients having the first occurrence of mild dyskaryosis. We evaluated the usefulness of this guideline and determined the positive predictive value (PPV) of conventional smears (CS) and ThinPrep samples (TP) reported as the first occurrence of mild dyskaryosis. Methods: This was a retrospective study where we looked at the cases of mild dyskaryosis from January’05 to June’05 received at our laboratory. Of these, the cases of mild dyskaryosis at the first instance were only taken into consideration. Histological diagnosis of these cases where available were retrieved from the laboratory database and were correlated with the cytological findings. Results: There were 1016 cases, which were reported as mild dyskaryosis. Out of them, 51.1% (519 cases) were first report of mild dyskaryosis: 61.8% (321 cases) and 38.2% (198 cases) were CS and TP respectively. Of these, 181 CS (56.4%) and 120 TP (60.6%) had a histological follow up. The results showed that 54.1% CS and 56.7% TP had a low‐grade outcome, 26.0% CS and 25.8% TP had a high‐grade outcome and 19.9% CS and 17.5% TP had a normal outcome. The PPV of mild dyskaryosis for CIN1 or worse result was 53.0% and 50.0% in CS and TP respectively. The PPV of mild dyskaryosis for CIN1 only was 27.1% and 24.2% in CS and TP respectively. Discussion: The difference in PPV for both systems is statistically insignificant. This result endorses usefulness of colposcopic referral after the first report of mild dyskaryosis.     

Nanocapsular Dispersion of Thymol for Enhanced Dispersibility and Increased Antimicrobial Effectiveness against Escherichia coli O157:H7 and Listeria monocytogenes in Model Food Systems

Essential oils are marginally soluble in water, making it challenging to evenly disperse them in foods and resulting in an increased tendency to bind with food lipids and proteins, resulting in lowered antimicrobial efficacy. In the current study, free and nano-dispersed (ND) thymol were compared in terms of their antimicrobial efficacies against Escherichia coli O157:H7 ATCC 43889 and 43894 and Listeria monocytogenes strains Scott A and 101 in apple cider and 2% reduced-fat milk. Apple cider was adjusted to pHs 5.5 and 3.5, and antimicrobial tests were performed at 0.3-, 0.5-, 0.75-, and 1.0-g/liter thymol concentrations at 35, 32, 25, and 4°C. Overall, 0.5 and 1.0 g/liter thymol in nano-dispersion and along with free thymol were inhibitory and bactericidal, respectively, against bacterial strains under all treatment conditions. At pH 5.5, 0.5 g/liter ND thymol was bacteriostatic against L. monocytogenes and E. coli for up to 48 h. At pH 3.5, L. monocytogenes controls did not survive beyond 12 h but E. coli survived and was inhibited by 0.5 g/liter ND thymol after 12 and 48 h in apple cider. E. coli strains were significantly sensitive to 4°C and pH 3.5 (P < 0.05). When bacteria were tested in 2% reduced-fat milk at 35 or 32°C, ND and free thymol demonstrated inhibition at 4.5 g/liter. Thus, the current technology seems to be promising and novel, enabling thymol-containing nano-dispersions that are not only transparent but also effective against pathogens in food applications, especially in clear beverages.     

Antioxidant Activity and Total Phenolic Content of Kale Genotypes Grown in Kashmir Valley

Green leafy vegetable extracts of six genotypes of kale (Brassica oleracea acephala) were evaluated for ascorbic acid, carotenoids, total phenolics and antioxidant activity. Ascorbic acid ranged from 142 mg per 100 g in Wappal Hakh to 164 mg per 100 g fr wt in Knol khol. Wild genotypes Wappal and Pumb, had significantly high phenolic content (285 and 227 mg per 100 g fr wt) and possessed highest antioxidant activities (840 and 780 µmol FRAP per g fr wt) than cultivated genotypes. A positive and strong correlation (R² = 0.807) between total phenolic content and antioxidant activity suggests that kale has enormous potential to enhance the antioxidant potential of our daily food supply. Wild genotypes, Wappal and Pumb can be incorporated into the breeding programmes in order to increase the antioxidant potential of cultivated varieties.     

Kir4.1 K+ channels are regulated by external cations

The inwardly rectifying potassium channel (Kir), Kir4.1 mediates spatial K(+)-buffering in the CNS. In this process the channel is potentially exposed to a large range of extracellular K(+) concentrations ([K(+)]o). We found that Kir4.1 is regulated by K(+)o. Increased [K(+)]o leads to a slow (mins) increase in the whole-cell currents of Xenopus oocytes expressing Kir4.1. Conversely, removing K(+) from the bath solution results in a slow decrease of the currents. This regulation is not coupled to the pHi-sensitive gate of the channel, nor does it require the presence of K67, a residue necessary for K(+)o-dependent regulation of Kir1.1. The voltage-dependent blockers Cs(+) and Ba(2+) substitute for K(+) and prevent deactivation of the channel in the absence of K(+)o. Cs(+) blocks and regulates the channel with similar affinity, consistent with the regulatory sites being in the selectivity-filter of the channel. Although both Rb(+) and NH4(+) permeate Kir4.1, only Rb(+) is able to regulate the channel. We conclude that Kir4.1 is regulated by ions interacting with specific sites in the selectivity filter. Using a kinetic model of the permeation process we show the plausibility of the channel's sensing the extracellular ionic environment through changes in the selectivity occupancy pattern, and that it is feasible for an ion with the selectivity properties of NH4(+) to permeate the channel without inducing these changes.     

Arabidopsis thaliana cdd1 mutant uncouples the constitutive activation of salicylic acid signalling from growth defects

Arabidopsis genotypes with a hyperactive salicylic acid-mediated signalling pathway exhibit enhanced disease resistance, which is often coupled with growth and developmental defects, such as dwarfing and spontaneous necrotic lesions on the leaves, resulting in reduced biomass yield. In this article, we report a novel recessive mutant of Arabidopsis, cdd1 (constitutive defence without defect in growth and development1), that exhibits enhanced disease resistance associated with constitutive salicylic acid signalling, but without any observable pleiotropic phenotype. Both NPR1 (NON-EXPRESSOR OF PATHOGENESIS-RELATED GENES1)-dependent and NPR1-independent salicylic acid-regulated defence pathways are hyperactivated in cdd1 mutant plants, conferring enhanced resistance against bacterial pathogens. However, a functional NPR1 allele is required for the cdd1-conferred heightened resistance against the oomycete pathogen Hyaloperonospora arabidopsidis. Salicylic acid accumulates at elevated levels in cdd1 and cdd1 npr1 mutant plants and is necessary for cdd1-mediated PR1 expression and disease resistance phenotypes. In addition, we provide data which indicate that the cdd1 mutation negatively regulates the npr1 mutation-induced hyperactivation of ethylene/jasmonic acid signalling.     

Analysis of the community structure of abyssal kinetoplastids revealed similar communities at larger spatial scales

Knowledge of the spatial scales of diversity is necessary to evaluate the mechanisms driving biodiversity and biogeography in the vast but poorly understood deep sea. The community structure of kinetoplastids, an important group of microbial eukaryotes belonging to the Euglenozoa, from all abyssal plains of the South Atlantic and two areas of the eastern Mediterranean was studied using partial small subunit ribosomal DNA gene clone libraries. A total of 1364 clones from 10 different regions were retrieved. The analysis revealed statistically not distinguishable communities from both the South-East Atlantic (Angola and Guinea Basin) and the South-West Atlantic (Angola and Brazil Basin) at spatial scales of 1000–3000 km, whereas all other communities were significantly differentiated from one another. It seems likely that multiple processes operate at the same time to shape communities of deep-sea kinetoplastids. Nevertheless, constant and homogenous environmental conditions over large spatial scales at abyssal depths, together with high dispersal capabilities of microbial eukaryotes, maintain best the results of statistically indistinguishable communities at larger spatial scales.     

Novel TNF-α converting enzyme (TACE) inhibitors as potential treatment for inflammatory diseases

Our research on hydantoin based TNF-α converting enzyme (TACE) inhibitors has led to an acetylene containing series that demonstrates sub-nanomolar potency (K(i)) as well as excellent activity in human whole blood. These studies led to the discovery of highly potent TACE inhibitors with good DMPK profiles.     

Analysis of beta-carotene hydroxylase gene cDNA isolated from the American oil-palm (Elaeis oleifera) mesocarp tissue cDNA library

It is well known that the nutritional quality of the American oil-palm (Elaeis oleifera) mesocarp oil is superior to that of African oil-palm (Elaeis guineensis Jacq. Tenera) mesocarp oil. Therefore, it is of important to identify the genetic features for its superior value. This could be achieved through the genome sequencing of the oil-palm. However, the genome sequence is not available in the public domain due to commercial secrecy. Hence, we constructed a cDNA library and generated expressed sequence tags (3,205) from the mesocarp tissue of the American oil-palm. We continued to annotate each of these cDNAs after submitting to GenBank/DDBJ/EMBL. A rough analysis turned our attention to the beta-carotene hydroxylase (Chyb) enzyme encoding cDNA. Then, we completed the full sequencing of cDNA clone for its both strands using M13 forward and reverse primers. The full nucleotide and protein sequence was further analyzed and annotated using various Bioinformatics tools. The analysis results showed the presence of fatty acid hydroxylase superfamily domain in the protein sequence. The multiple sequence alignment of selected Chyb amino acid sequences from other plant species and algal members with E. oleifera Chyb using ClustalW and its phylogenetic analysis suggest that Chyb from monocotyledonous plant species, Lilium hubrid, Crocus sativus and Zea mays are the most evolutionary related with E. oleifera Chyb. This study reports the annotation of E. oleifera Chyb. ABBREVIATIONS: ESTs - expressed sequence tags, EoChyb - Elaeis oleifera beta-carotene hydroxylase, MC - main cluster.     

Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map

Olfactory sensory neurons expressing a given odorant receptor (OR) project with precision to specific glomeruli in the olfactory bulb, generating a topographic map. In this study, we demonstrate that neurons expressing different ORs express different levels of ephrin-A protein on their axons. Moreover, alterations in the level of ephrin-A alter the glomerular map. Deletion of the ephrin-A5 and ephrin-A3 genes posteriorizes the glomerular locations for neurons expressing either the P2 or SR1 receptor, whereas overexpression of ephrin-A5 in P2 neurons results in an anterior shift in their glomeruli. Thus the ephrin-As are differentially expressed in distinct subpopulations of neurons and are likely to participate, along with the ORs, as one of a complement of guidance receptors governing the targeting of like axons to precise locations in the olfactory bulb.     

Adsorption Optimization of Lead (II) Using Saccharum Bengalense as a Non-Conventional Low Cost Biosorbent: Isotherm and Thermodynamics Modeling

In the present study a novel biomass, derived from the pulp of Saccharum bengalense, was used as an adsorbent material for the removal of Pb (II) ions from aqueous solution. After 50 minutes contact time, almost 92% lead removal was possible at pH 6.0 under batch test conditions. The experimental data was analyzed using Langmuir, Freundlich, Timken and Dubinin-Radushkevich two parameters isotherm model, three parameters Redlich—Peterson, Sip and Toth models and four parameters Fritz Schlunder isotherm models. Langmuir, Redlich—Peterson and Fritz-Schlunder models were found to be the best fit models. Kinetic studies revealed that the sorption process was well explained with pseudo second-order kinetic model. Thermodynamic parameters including free energy change (ΔG°), enthalpy change (ΔH°) and entropy change (ΔS°) have been calculated and reveal the spontaneous, endothermic and feasible nature of the adsorption process. The thermodynamic parameters of activation (ΔG ^#, ΔH ^#and ΔS ^#) were calculated from the pseudo-second order rate constant by using the Eyring equation. Results showed that Pb (II) adsorption onto SB is an associated mechanism and the reorientation step is entropy controlled.