Theory for designing mechanically stable single- and double-walled SiGe nanopeapods

Journal of Molecular Modeling - The adsorption and inhibition mechanism of chain length increase and group substitution of imidazole tetrafluoroborate derivatives for the corrosion inhibition of...     

Eye lens and thyroid gland radiation exposure for patients undergoing brain computed tomography examination

This study aims to estimate the effective radiation dose and organ dose from head CT procedures. It was conducted in three main private hospitals in Khartoum State-Sudan, using Toshiba machines with 64 slices. The total number of patients included in this study was 142 patients (82 males and 60 females). The effective dose and organ dose were calculated by CT Expo software. The effective dose slightly varied among patients according to gender and age. The effective dose for female patients (5.99 mSv) was higher than that for male patients (5.84 mSv), and the pediatric dose (5.46 mSv) was lower than the adults’ dose (5.94 mSv).The dose for eye lens was found lower for male patients (89.117 mSv) than the dose for female patients (94.62) mSv). According to patients’ age: the dose received by the lens of the eye was much lower in pediatric (79.93 mSv) than the adults (92.41 mSv). The dose for thyroid in female patients (33.52 mSv) was higher than the male patients (28 mSv). The pediatric dose (28.34 mSv) was lower than the adults’ dose (30.64 mSv).Departmental imaging protocol and lack of training among hospital staff are expected to be responsible for these variations. Therefore, this study recommends that the CT technologists be trained on suitable strategies to achieve dose optimization. Moreover, patients’ doses must be monitored regularly.     

Ancistrolikokine D,a 5,8'-coupled naphthylisoquinoline alkaloid,and related natural products from Ancistrocladus likoko

A new naphthylisoquinoline alkaloid, ancistrolikokine D, and the likewise 5,8'-coupled alkaloid ancistroealaine A, as well as two further, biosynthetically related, but nitrogen-free natural products, ancistronaphthoic acid B and cis-isoshinanolone, have been isolated from Ancistrocladus likoko J. LEACUTE;ONARD (Ancistrocladaceae). The 5,8'-coupling of the new alkaloids and of the alkaloids isolated earlier hints at a close phylogenetic relationship of A. likoko to other Central African Ancistrocladus species. The compounds show moderate activities against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei rhodesiense.     

Making Activity Recognition Robust against Deceptive Behavior

Healthcare services increasingly use the activity recognition technology to track the daily activities of individuals. In some cases, this is used to provide incentives. For example, some health insurance companies offer discount to customers who are physically active, based on the data collected from their activity tracking devices. Therefore, there is an increasing motivation for individuals to cheat, by making activity trackers detect activities that increase their benefits rather than the ones they actually do. In this study, we used a novel method to make activity recognition robust against deceptive behavior. We asked 14 subjects to attempt to trick our smartphone-based activity classifier by making it detect an activity other than the one they actually performed, for example by shaking the phone while seated to make the classifier detect walking. If they succeeded, we used their motion data to retrain the classifier, and asked them to try to trick it again. The experiment ended when subjects could no longer cheat. We found that some subjects were not able to trick the classifier at all, while others required five rounds of retraining. While classifiers trained on normal activity data predicted true activity with ~38% accuracy, training on the data gathered during the deceptive behavior increased their accuracy to ~84%. We conclude that learning the deceptive behavior of one individual helps to detect the deceptive behavior of others. Thus, we can make current activity recognition robust to deception by including deceptive activity data from a few individuals.     

Synthesis and biological testing of novel pyridoisothiazolones as histone acetyltransferase inhibitors

We present a combination of database screening, synthesis and in vitro testing to identify novel histone acetyltransferase (HAT) inhibitors. The National Cancer Institute compound collection (NCI) and several commercial databases were filtered by similarity-based virtual screening to find new HAT inhibitors. Employing the recombinant HAT p300/CBP-associated factor (PCAF) and two different histone substrates for screening, pyridoisothiazolones were identified as inhibitors of human PCAF. Due to the limited solubility of the initial hits, we synthesized and tested them on PCAF. The compounds inhibit the proliferation of cancer cells. In summary, valuable chemical tools and potential lead candidates for new anticancer agents directed against HATs as new targets have been identified.     

From cosubstrate similarity to inhibitor diversity--inhibitors of ADP-ribosyltransferases from kinase inhibitor screening

ADP-ribosyltransferases (ADP-RTs) use NAD(+) to transfer an ADP-ribosyl group to target proteins. Although some ADP-RTs are bacterial toxins only few inhibitors are known. Here we present the development of fluorescence-based assays and a focussed library screening using kinase inhibitors as a new approach towards inhibitors of ADP-RTs. Different screening setups were established using surrogate small molecule substrates or the quantitation of the cofactor NAD(+). Proof-of-principle screening experiments were performed using a kinase inhibitor library in order to target the NAD(+) binding pockets. This led to the discovery of structurally different lead inhibitors for the mono-ADP-ribosyltransferases Mosquitocidal toxin (MTX) from Bacillus sphaericus SSII-1, C3bot toxin from Clostridium botulinum and CDTa from Clostridium difficile. The interaction of the inhibitors with the toxin proteins was analyzed by means of docking and binding free energy calculations. Binding at the nicotinamide subpocket, which shows a significant difference in the three enzymes, is used to explain the selectivity of the identified inhibitors and offers an opportunity for further development of potent and selective inhibitors.     

Chemoprotective effects of carnosine against genotoxicity induced by cyclophosphamide in mice bone marrow cells

The protective effects of carnosine as a natural dipeptide were investigated in mouse bone marrow cells against genotoxicity induced by cyclophosphamide. Mice were injected with solutions of carnosine at three different doses (10, 50 and 100?mg kg(-1) bw) for five consecutive days. On the fifth day of treatment, mice were injected cyclophosphamide and killed after 24?h. The frequency of micronuclei in polychromatic erythrocytes and the ratio of polychromatic erythrocyte/polychromatic erythrocyte?+?normochromatic erythrocyte [PCE/(PCE?+?NCE)] were evaluated by May-Grunwald/Giemsa staining. Histopathology of bone marrow was examined in mice treated with cyclophosphamide and carnosine. Carnosine significantly reduced micronucleated polychromatic erythrocytes (MnPCEs) induced by cyclophosphamide at all three doses. Carnosine at dose of 100?mg kg(-1) bw reduced MnPCEs 3.76-fold and completely normalized the PCE/(PCE?+?NCE) ratio. Administration of carnosine inhibited bone marrow toxicity induced by cyclophosphamide. It appeared that carnosine with protective activity reduced the oxidative stress and genotoxicity induced by cyclophosphamide in bone marrow cells of mice. Copyright ? 2012 John Wiley & Sons, Ltd.     

Cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver. A fraction of adenosine bound is converted to adenine.

1. Adenosine bound to the cyclic AMP-adenosine binding protein/S-adenosylhomocysteinase from mouse liver was partly converted to a product which was identified as adenine in four chromatographic systems. Ribose was formed in equivalent amounts. 2. The time course of the reaction was characterized by an initial burst phase lasting for less than one second followed by a slow progressive phase. The reaction was partly reversed by prolonged incubation, slow denaturation of the protein, dilution of the incubation mixture and removal of adenosine by converting it to inosine by the enzyme adenosine deaminase. 3. Both the ATP-treated (Ueland, P.M. and D?skeland, S.O. (1978) Arch. Biochem. Biophys. 185, 195--203) and the non-treated protein were subjected to polyacrylamide gel electrophoresis at pH 8.8. The adenosine-adenine, the cyclic AMP binding activities and the conversion activity comigrated with the main protein band, indicating that these properties reside on the same protein molecule. 4. Adenine generated by hydrolysis of adenosine was mainly bound to the protein as judged by nearly complete reversion of the conversion upon dilution in the presence of excess unlabelled adenine and by Sephadex G-25 chromatography. 5. The conversion of adenosine to inosine by the enzyme adenosine deaminase was decreased in the presence of the binding protein. 6. Adenine formation could also be demonstrated under condition of enzymic formation of S-adenosylhomocysteine, i.e. in the presence of hymocysteine.     

Genetic variation and relationships between isolates and species of the entomopathogenic nematode genus Heterorhabditis deciphered through isozyme profiles

We studied variation in isozyme patterns of 8 metabolic enzymes in 5 species of Heterorhabditis (H. bacteriophora, H. indica, H. marelata, H. megidis, and H. zealandica) comprising 18 isolates. Isozyme banding patterns of all the 8 enzymes were species specific; however, 3 enzymes, i.e., arginine kinase, fumarate hydratase, and malate dehydrogenase, displayed distinct patterns among all the 18 isolates. Phylogenetic analysis of the isozyme patterns produced dendrograms depicting a high degree of genetic variation among Heterorhabditis species, with the average pairwise distance of 0.2000. Trees constructed using different phylogenetic methods showed a relatively close genetic relationship between H. megidis and H. zealandica and between H. bacteriophora and H. indica. Also, H. bacteriophora HP88 was the most distant species from H. megidis (UK isolate), H. marelatus (Oregon isolate), and H. zealandica (X1 isolate) with pairwise distance of 0.1957, 0.2228, and 0.2120, respectively. Phylogenetic analysis also revealed genetic variation among H. bacteriophora isolates with the average pairwise distance of 0.1507. GPS2 and GPS3 were the most closely related isolates with the average distance of only 0.0870, followed by GPS1 and GPS2 with average distance of 0.1087. In contrast, KMD19 and HP88, OH25, and HP88, and OH25 and Acows isolates were the most divergent populations with a pairwise distance of 0.2011 and 37 character differences. Pairwise distance analysis also revealed that genetic divergence among populations of H. bacteriophora is relatively independent of geographic distance. Overall, these results demonstrate strong subspecies structuring in H. bacteriophora.     

Glypican 4 mediates Wnt transport between germ layers via signaling filopodia

Glypicans influence signaling pathways by regulating morphogen trafficking and reception. However, the underlying mechanisms in vertebrates are poorly understood. In zebrafish, Glypican 4 (Gpc4) is required for convergence and extension (C&E) of both the mesoderm and endoderm. Here, we show that transgenic expression of GFP-Gpc4 in the endoderm of gpc4 mutants rescued C&E defects in all germ layers. The rescue of mesoderm was likely mediated by Wnt5b and Wnt11f2 and depended on signaling filopodia rather than on cleavage of the Gpc4 GPI anchor. Gpc4 bound both Wnt5b and Wnt11f2 and regulated formation of the filopodia that transport Wnt5b and Wnt11f2 to neighboring cells. Moreover, this rescue was suppressed by blocking signaling filopodia that extend from endodermal cells. Thus, GFP-Gpc4–labeled protrusions that emanated from endodermal cells transported Wnt5b and Wnt11f2 to other germ layers, rescuing the C&E defects caused by a gpc4 deficiency. Our study reveals a new mechanism that could explain in vivo morphogen distribution involving Gpc4.