A murine genital-challenge model is a sensitive measure of protective antibodies against human papillomavirus infection

The available virus-like particle (VLP)-based prophylactic vaccines against specific human papillomavirus (HPV) types afford close to 100% protection against the type-associated lesions and disease. Based on papillomavirus animal models, it is likely that protection against genital lesions in humans is mediated by HPV type-restricted neutralizing antibodies that transudate or exudate at the sites of genital infection. However, a correlate of protection was not established in the clinical trials because few disease cases occurred, and true incident infection could not be reliably distinguished from the emergence or reactivation of prevalent infection. In addition, the current assays for measuring vaccine-induced antibodies, even the gold standard HPV pseudovirion (PsV) in vitro neutralization assay, may not be sensitive enough to measure the minimum level of antibodies needed for protection. Here, we characterize the recently developed model of genital challenge with HPV PsV and determine the minimal amounts of VLP-induced neutralizing antibodies that can afford protection from genital infection in vivo after transfer into recipient mice. Our data show that serum antibody levels >100-fold lower than those detectable by in vitro PsV neutralization assays are sufficient to confer protection against an HPV PsV genital infection in this model. The results clearly demonstrate that, remarkably, the in vivo assay is substantially more sensitive than in vitro PsV neutralization and thus may be better suited for studies to establish correlates of protection.     

Electrophysiological Indices of Response Inhibition in a Go/NoGo Task Predict Self-Control in a Social Context

Recent research demonstrates that response inhibition—a core executive function—may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test). Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes—two established electrophysiological indices of response inhibition—both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.     

The Heart in Diabetes

Since the introduction of insulin, heart disease has become a major impediment to survival in persons with diabetes mellitus. Coronary disease has increased severity and accelerated development in diabetic persons compared with an age- and sex-matched nondiabetic population. A peculiar vulnerability of women to the influence of diabetes with loss of premenopausal coronary disease protection has been found. The symptomatology of coronary events may differ and coronary care data show a higher incidence of sudden death in diabetic patients who have a myocardial infarction than in their non-diabetic counterparts. Insulin may play a role in the myocardial adjustment to an ischemic insult by enhancing glucose intake and suppressing lipolysis and ketogenesis. Carbohydrate intolerance in dogs, rhesus monkeys and humans appears associated with similar histologic and compositional changes in the myocardium. Abnormalities in diastolic ventricular function not attributable to large- or small-vessel coronary disease have been found in the diabetic subjects of each species. Studies in humans who have diabetes have assessed single pressure-volume relationships and more exacting measures of ventricular compliance are needed. Abnormalities of myocardial function in patients with diabetes have been found using echo and radionuclide techniques. Many of these findings need to be correlated with invasive data or confirmed in larger populations. Autonomic dysfunction is common in diabetic persons and may imply an associated poor prognosis. Reflex abnormalities in parasympathetic function are most prevalent and occur before sympathetic dysfunction.     

Untersuchungen über die Embryogenie in der GattungGnaphalium

Ohne Zusammenfassung     

A novel cyclic opioid peptide analog showing high preference for mu-receptors

The side-chain to side-chain cyclized opioid peptide analogs H-Tyr-D-Orn-Phe-Asp-NH2 (I) and H-Tyr-D-Lys-Phe-Glu-NH2 (II) were synthesized and tested in the guinea pig ileum and mouse vas deferens assays and in binding assays based on displacement of mu- and delta-opioid receptor-selective radioligands from rat brain membranes. The more rigid cyclic analog I containing a 13-membered ring structure showed very high preference for mu-receptors over delta-receptors, whereas the more flexible cyclic peptide II (15-membered ring) was non-selective. These results indicate that variation in the degree of conformational restriction of opioid peptides can produce drastic shifts in their receptor selectivity profile. Because of its high mu-receptor selectivity and rigidity cyclic analog I will be useful for determining the conformational requirements of mu-opioid receptors.