QSAR-aided in silico approach in evaluation of food proteins as precursors of ACE inhibitory peptides

An increasing prevalence of hypertension in the world implies the necessity of further study of antihypertensive peptides as an alternative means for hypertension management. The purpose of this study was to evaluate systematically the potential of major food proteins as precursors of ACE inhibitory peptides using QSAR-aided in silico approach, and thus to establish the rationale for choosing the appropriate substrate proteins in preparing ACE inhibitory peptides. In silico digestion of proteins from 15 common food commodities by thermolysin generated 5709 peptides ranging from 2 to 6 amino acid residues. Peptides were divided into three categories based on the potency of their predicted activities. Our results showed that meat proteins from pork, beef and chicken contain the largest number of potent peptides (IC₅₀ < 10 ??M), followed by proteins from milk, egg, soybean and canola, whereas proteins from fish (with the exception of salmon) and cereals (oat and barley) contain the least number of potent peptides. This study demonstrated that proteins from livestock meat, milk, egg, soybean and canola are good sources of ACE inhibitory peptides.     

Ultra-thin graphene edges at the nanowire tips: a cascade cold cathode with two-stage field amplification

A multistage field emitter based on graphene-linked ZnO nanowire array is realized by means of spin-coating a graphene dispersion (reduced graphene oxide) over a nanostructured platform followed by plasma modification. Spin-coating leads to interlinking of graphene sheets between the neighboring nanowires whereas plasma etching in the subsequent step generates numerous ultra-sharp graphene edges at the nanowire tips. The inherent tendency of graphene to lay flat over a plane substrate can easily be bypassed through the currently presented nanostructure platform based technique. The turn-on and threshold field significantly downshifted compared to the individual components in the cascade emitter. Through the facile electron transfer from nanowires to graphene due to band bending at the ZnO-graphene interface together with multistage geometrical field enhancement at both the nanowire and graphene edges remain behind this enriched field emission from the composite cold cathode. This strategy will open up a new direction to integrate the functionalities of both the graphene array and several other inorganic nanostructure array for practical electronic devices.     

Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis

The contributions of 23 insertion, deletion, or missense mutations within an 81-bp fragment of rpoB, the gene encoding the beta-subunit of the DNA-dependent RNA polymerase of Mycobacterium tuberculosis, to the development of resistance to rifamycins (rifampin, rifabutin, rifapentine, and KRM-1648) in 29 rifampin-resistant clinical isolates were defined. Specific mutant rpoB alleles led to the development of cross-resistance to all rifamycins tested, while a subset of mutations were associated with resistance to rifampin and rifapentine but not to KRM-1648 or rifabutin. To further study the impact of specific rpoB mutant alleles on the development of rifamycin resistance, mutations were incorporated into the rpoB gene of M. tuberculosis H37Rv, contained on a mycobacterial shuttle plasmid, by in vitro mutagenesis. Recombinant M. tuberculosis clones containing plasmids with specific mutations in either codon 531 or 526 of rpoB exhibited high-level resistance to all rifamycins tested, whereas clones containing a plasmid with a mutation in codon 516 exhibited high-level resistance to rifampin and rifapentine but were susceptible to both rifabutin and KRM-1648. These results provided additional proof of the association of specific rpoB mutations with the development of rifamycin resistance and corroborate previous reports of the usefulness of rpoB genotyping for predicting rifamycin-resistant phenotypes.     

Ultrasound screening for deep venous thrombosis after total knee arthroplasty. 2-year reassessment

The efficacy of ultrasound compared with ascending venography for the detection of deep venous thrombosis immediately after total knee arthroplasty was assessed after a 2-year interval. One hundred thirty-seven patients were eligible for the study; however, 31 patients received only one of the screening methods and a color Doppler examination was inconclusive in six patients. Therefore, 100 patients had a Doppler examination and a venogram. Overall, the sensitivity of ultrasound was 85%, the specificity 97%, the positive predictive value 85%, the negative predictive value 97%, and the accuracy 95%. The sensitivity in the calf was 83%, in the popliteal vein 86%, and in the femoral vein 100%. Two years ago, the initial assessment of ultrasound for the detection of deep venous thrombosis after surgery in patients who had total joint arthroplasty revealed a 75% sensitivity, 99% specificity, 91% positive predictive value, 97% negative predictive value, and 97% accuracy. The sensitivity in the calf was 83%; the sensitivity in the popliteal vein was 40%; and the sensitivity in the femoral vein was 50%. After 2 years of using this screening test with one technician and one radiologist, an improvement with this noninvasive technique was shown. However, it was found that Doppler imaging is not as sensitive as venography for detecting calf thrombi. Any imaging technique should be validated by each institution to determine the validity of the instrument and the learning curve of the technician administering the examination.     

Palmitoylated cysteine 341 modulates phosphorylation of the beta2-adrenergic receptor by the cAMP-dependent protein kinase

We previously showed that substitution of a glycine residue for the palmitoylated cysteine 341 of the human beta2-adrenergic receptor (Gly341beta2AR), increases the basal level of the receptor phosphorylation and reduces its ability to functionally interact with Gs. In the present study, we show that additional mutation of serines 345 and 346 (Ala345,346Gly341beta2AR) restored normal phosphorylation and receptor-Gs coupling, thus suggesting that the increased phosphorylation of this site, rather than the lack of palmitoylation per se, is responsible for the poor coupling of the unpalmitoylated receptor. This is supported by the observation that chemical depalmitoylation of purified beta2AR did not affect the ability of the receptor to stimulate adenylyl cyclase in reconstitution assays. Furthermore, mutation of Ser345,346 in a wild type receptor background (Ala345,346beta2AR) significantly decreased the rate of agonist-promoted desensitization of the receptor-stimulated adenylyl cyclase activity, supporting a role for this phosphorylation site in regulating the functional coupling of the receptor. Since serines 345 and 346 are located in a putative cyclic AMP-dependent protein kinase (PKA) phosphorylation site immediately downstream of the palmitoylated cysteine 341, the hypothesis that the accessibility of this site may be regulated by the receptor palmitoylation state was further assessed in vitro. In membrane phosphorylation assays, Gly341beta2AR was found to be a better substrate for PKA than the wild type receptor, thus supporting the notion that palmitoylation restrains access of the phosphorylation site to the enzyme. Taken together, the data demonstrate that palmitoylation of cysteine 341 controls the phosphorylation state of the PKA site located in the carboxyl tail of the beta2AR and by doing so modulates the responsiveness of the receptor.     

An NSF-like ATPase, p97, and NSF mediate cisternal regrowth from mitotic Golgi fragments

Golgi cisternae regrew in a cell-free system from mitotic Golgi fragments incubated with buffer alone. Pretreatment with NEM or salt washing inhibited regrowth, but this could be restored either by p97, an NSF-like ATPase, or by NSF together with SNAPs and p115, a vesicle docking protein. The morphology of cisternae regrown with p97 and NSF-SNAPs-p115 differed, suggesting that they play distinct roles in rebuilding Golgi cisternae after mitosis.     

Prevalence of teaching apical patency and various instrumentation and obturation techniques in United States dental schools

Maintaining an open apex beyond the apical constriction with an endodontic file during canal instrumentation is a concept that has been advocated by several authors and clinicians. To ascertain the prevalence of teaching the patency concept as well as various instrumentation and obturation techniques in the United States dental schools, a survey was conducted. Forty-eight out of a total of 53 dental schools (91%) responded to the survey. Results indicate that 50% of the schools surveyed teach the concept of patency to their undergraduates or graduates or both; 83% teach a step-back instrumentation technique; and 89.6% teach lateral condensation of gutta percha as their primary obturation technique.