Small, anionic, and charge-neutralizing propeptide fragments of zymogens are antimicrobial

Some inactive precursor proteins, or zymogens, contain small, amino terminus, homopolymeric regions of Asp that neutralize the cationic charge of the active protein during synthesis. After posttranslational cleavage, the anionic propeptide fragment may exhibit antimicrobial activity. To demonstrate this, ovine trypsinogen activation peptide, and frog (Xenopus laevis) PYL activation peptide, both containing homopolymeric regions of Asp, were synthesized and tested against previously described surfactant-associated anionic peptide. Peptides inhibited the growth of both gram-negative (MIC, 0.08 to 3.00 mM) and gram-positive (MIC, 0.94 to 2.67 mM) bacteria. Small, anionic, and charge-neutralizing propeptide fragments of zymogens form a new class of host-derived antimicrobial peptides important in innate defense.     

Tyrosine 112 of latent membrane protein 2A is essential for protein tyrosine kinase loading and regulation of Epstein-Barr virus latency

Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) is expressed on the plasma membrane of B lymphocytes latently infected with EBV and blocks B-cell receptor (BCR) signal transduction in EBV-immortalized B cells in vitro. The LMP2A amino-terminal domain that is essential for the LMP2A-mediated block on BCR signal transduction contains eight tyrosine residues. Association of Syk protein tyrosine kinase (PTK) with LMP2A occurs at the two tyrosines of the LMP2A immunoreceptor tyrosine-based activation motif, and it is hypothesized that Lyn PTK associates with the YEEA amino acid motif at LMP2A tyrosine 112 (Y112). To examine the specific association of Lyn PTK to LMP2A, a panel of LMP2A cDNA expression vectors containing LMP2A mutations were transfected into an EBV-negative B-cell line and analyzed for Lyn and LMP2A coimmunoprecipitation. Lyn associates with wild-type LMP2A and other LMP2A mutant constructs, but Lyn association is lost in the LMP2A construct containing a tyrosine (Y)-to-phenylalanine (F) mutation at LMP2A residue Y112 (LMP2AY112F). Next, the LMP2AY112F mutation was recombined into the EBV genome to generate stable lymphoblastoid cell lines (LCLs) transformed with the LMP2AY112F mutant virus. Analysis of BCR-mediated signal transduction in the LMP2AY112F LCLs revealed loss of the LMP2A-mediated block in BCR signal transduction. In addition, LMP2A was not tyrosine phosphorylated in LMP2AY112F LCLs. Together these data indicate the importance of the LMP2A Y112 residue in the ability of LMP2A to block BCR-mediated signal transduction and place the role of this residue and its interaction with Lyn PTK as essential to LMP2A phosphorylation, PTK loading, and down-modulation of PTKs involved in BCR-mediated signal transduction.     

Social-cognitive influences on change in aggression over time.

This study examined whether social cognitions that have been assumed to influence aggression actually forecast change in aggressive habits over time. Participants were 189 3rd- through 7th-grade boys and girls; data on social cognitions and social behaviors were collected in the fall and spring of the school year. Aggression-encouraging cognitions assessed in the fall indeed promoted aggression over the school year, but such developments hinged critically on child sex and on initial (fall) levels of aggression and victimization. Results illustrate the principle that cognitions affect behavioral development mainly when the child's transactions with the social environment support the use of the cognitions as guides for behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chromosome 1p terminal deletion: report of new findings and confirmation of two characteristic phenotypes

We report three unrelated patients with small terminal deletions involving 1p36.22-->pter that occurred de novo and compare our patients to the 10 previously reported cases. Although our patients have an identical cytogenetic deletion, patients 1 and 2 share similar clinical features that differ substantially from patient 3. Our patients confirm the existence of two characteristic phenotypes in 1p36.22-->pter deletion. Both phenotypes share some dysmorphic features, but are differentiated by characteristics of growth failure versus macrosomia. In addition, we report the new finding of cardiomyopathy and hydrocephalus in the phenotype associated with growth failure. It is possible that different phenotypic subgroups may exist because of differences in the parental origins of the deleted chromosome or of variations in undetectable amounts of genetic material.     

Prosthetic arteriovenous fistulas and venous anastomotic stenosis: influence of a high flow velocity on the development of intimal hyperplasia

OBJECTIVE: To search a sensitive parameter for the early diagnosis of primary open angle glaucoma (POAG). METHOD: A system of computerized image analysis was used to acquire images of the optic nerve head of patients with POAG, suspect glaucoma (SG) and of normal persons. Each of these groups contained 31 eyes of 31 cases. The mean relative depths of disc rim and cup at different areas in the optic nerve head were measured. All these patients were followed up for four to six months, and the changes of the mean depths of every sector were compared between each pair of the three groups with statistic analysis. RESULTS: The mean depth of the neural rim and cup of each sector and that of total rim and total cup of POAG and SG patients were all deeper than that of normal controls. The mean depths of neural rim of the superior sector, inferior sector and the total rim area of POAG were deeper than that of SG patients. Compared to their first measurements, the changes of mean depths of neural rim of superior sector and total neural rim area of POAG patients were more prominent than that of normal controls and SG. We also compared the relative depth of the total rim area in the different areas in the optic nerve head with other two dimensional optic disc parameters such as cup/disc ratio, etc. CONCLUSION: Our study suggests that three-dimensional stereoscopic measurement of the surface of optic nerve head and follow-up be of paramount importance in the early diagnosis of POAG patients.     

Impaired endothelium-dependent relaxation in isolated resistance arteries of spontaneously diabetic rats

1. Previous studies have shown that endothelium-dependent relaxation in the aorta of spontaneously diabetic bio bred rats (BB) is impaired. 2. We have investigated noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) and bradykinin (BK) relaxation, and endothelium-independent sodium nitroprusside (SNP) relaxation in mesenteric resistance arteries of recent onset BB rats and established insulin treated BB rats, compared to their age-matched non diabetic controls. 3. There was no significant difference in the maximum contractile response or sensitivity to noradrenaline in either of the diabetic groups compared to their age-matched controls. 4. Incubation with the nitric oxide synthetase inhibitor NG-nitro-L-arginine (L-NOARG) resulted in a significant increase in maximum contractile response to noradrenaline in the recent onset age-matched control group (P < 0.05). Analysis of the whole dose-response curve (using ANOVA for repeated measures with paired t test) showed a significant left-ward shift following the addition of L-NOARG (P < 0.001). A similar but less marked shift (P < 0.01) was evident in vessels from recent onset diabetics. An overall shift in both sensitivity and maximum response was also evident in the age-matched non diabetic controls of the insulin-treated group (P < 0.05). However, by contrast, there was no significant change in sensitivity in the insulin-treated diabetic rats. 5. ACh-induced endothelium-dependent relaxation was significantly impaired in the recent onset diabetic rats compared to their age-matched controls (47 +/- 11% versus 92 +/- 2%, P < 0.05, n = 6), and in the insulin treated diabetic rats (34 +/- 5% versus 75 +/- 6%, P < 0.05, n = 6). The relaxation responses to BK also were significantly impaired in the diabetic rats compared to their age-matched controls (recent onset: 20 +/- 3% versus 72 +/- 7%, P < 0.05, n = 6; insulin treated: 12 +/- 9% versus 68 +/- 7%, P < 0.05, n = 7). 6. Incubation with either the nitric oxide synthetase substrate, U-arginine, or the free radical scavenging enzyme superoxide dismutase (150 mu ml-1) failed to improve the attenuated response of acetylcholine-induced relaxation in the diabetic vessels. 7. Endothelium-dependent relaxation mediated by ACh and BK was significantly attenuated in both the diabetic and control vessels after incubation with L-NOARG. 8. Pretreatment with a cyclo-oxygenase inhibitor, indomethacin, significantly enhanced the relaxation to ACh in both the recent onset and insulin treated diabetic rats (42 +/- 10%, n = 7 versus 64 +/- 7%, n = 7, P < 0.05, and 40 +/- 5%, n = 7 versus 65 +/- 9%, n = 6, P < 0.05). 9. Following endothelium removal, there was a marked impairment in endothelium-dependent relaxation responses to ACh and BK in both the diabetic and control vessels. 10. Incubation with the thromboxane A2 receptor antagonist SQ29548, did not significantly improve the ACh endothelium-dependent relaxation response in the diabetic vessels. 11. Endothelium-independent relaxation to sodium nitroprusside was significantly impaired in the first group of diabetic vessels studied; however, subsequent studies showed no impairment of the sodium nitroprusside response in the diabetic vessels. 12. In conclusion, the ability of the endothelium to regulate vascular contractility is reduced in recent onset diabetic vessels, and significantly impaired in established insulin treated diabetics. Relaxation to the endothelium-dependent vasodilators ACh and BK was impaired in both the recent onset and the established insulin treated diabetics, and the ACh response was significantly improved following pretreatment with indomethacin, suggesting a role for a cyclo-oxygenase-derived vasoconstrictor. Preliminary studies with a thromboxane A2, receptor antagonist, SQ29548 did not significantly improve the impaired relaxation to ACh, indicating that the vasoconstrictor prostanoid is not thromboxane A2.     

What students say about learning and teaching in longitudinal ambulatory primary care clerkships: a multi-institutional study

The past year has seen a coming-of-age in DNA enzyme research. Far from being laboratory curiosities, the activities of new DNA enzymes have broadened the known catalytic repertoire of nucleic acid enzymes, provided valuable insights into different mechanistic possibilities open to nucleic acid catalysts, and explored the importance for catalysis of native functionalities within DNA and RNA, as well as of a diversity of extrinsic cofactors. Thus, the first amino acid cofactor-utilizing DNA enzyme has been described, as well as DNA enzymes that cleave RNA without the assistance of any external cofactor. On the practical side, the most efficient RNA-cleaving nucleic acid enzyme described to date is a DNA enzyme.     

Calibration of Comprehension: Research and Implications for Education and Instruction

The ability to accurately evaluate one's understanding of text information is critical for optimum learning to take place. One widely used paradigm for examining the accuracy of individuals' self-assessed comprehension has been termed calibration of comprehension. In this paradigm, students read a passage and are asked to make predictions about their future performance on a comprehension test. Calibration of comprehension is the relation between students' confidence and performance or between predicted and actual performance. In the present paper we review research on calibration of comprehension, examining a number of variables that have been found to influence calibration ability. In the first three sections of our paper we focus on the effects of individual, task, and text variables on students' calibration of comprehension. In the final section, we discuss implications of research on calibration for education and instruction. Copyright 1998 Academic Press.     

Respiratory effects of intravenous midazolam

Thirty-four healthy, young-adult patients receiving intravenous midazolam for third-molar surgery had their respiratory parameters measured by respiratory inductive plethysmography. Tidal volume and minute volume showed significant changes during the initial 5-10 minutes of sedation, the changes being maximal during the first 5 minutes from the completion of injection of midazolam. The measurement of phase angle, an indicator of respiratory asynchrony, showed no significant change from normal, although a few patients showed some asynchrony of breathing, suggesting some amount of respiratory obstruction. A few patients showed a short period of apnoea and a small fall in the oxygen saturation. None of these changes caused any clinical concerns. It is suggested that the absence of stimulation after injection of midazolam, particularly in the initial few minutes, may contribute to the potential onset of respiratory problems.