Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy

Retrograde transport from the Golgi to the ER is an essential process. Resident ER proteins that escape the ER and proteins that cycle between the Golgi and the ER must be retrieved. The interdependence of anterograde and retrograde vesicle trafficking makes the dissection of both processes difficult in vivo. We have developed an in vitro system that measures the retrieval of a soluble reporter protein, the precursor of the yeast pheromone alpha-factor fused to a retrieval signal (HDEL) at its COOH terminus (Dean, N., and H.R.B Pelham. 1990. J. Cell Biol. 111:369-377). Retrieval depends on the HDEL sequence; the alpha-factor precursor, naturally lacking this sequence, is not retrieved. A full cycle of anterograde and retrograde transport requires a simple set of purified cytosolic proteins, including Sec18p, the Lma1p complex, Uso1p, coatomer, and Arf1p. Among the membrane-bound v-SNAP receptor (v-SNARE) proteins, Bos1p is required only for forward transport, Sec22p only for retrograde trafficking, and Bet1p is implicated in both avenues of transport. Putative retrograde carriers (COPI vesicles) generated from Golgi-enriched membranes contain v-SNAREs as well as Emp47p as cargo.     

Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library

An encoded 13,020-member combinatorial library was synthesized containing a statine core. Evaluation of this library with plasmepsin II, an aspartyl protease required for hemoglobin metabolism in the malaria parasite, led to the identification of potent and selective inhibitors as well as novel structure-activity relationships.     

Plasmalemmal pH-gradients in drug-sensitive and drug-resistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy

31p Magnetic resonance spectroscopy (MRS) was employed to investigate tumor pH in xenografts of drug-sensitive and drug-resistant MCF-7 human breast carcinoma cells. Measured extracellular pH values were found to be lower than the intracellular pH in all three tumor types investigated. The magnitude of this acid-outside plasmalemmal pH gradient increased with increasing tumor size in tumors of two drug-resistant variants of MCF-7 cells, but not in tumors of the parent (drug-sensitive) cells. The partitioning of weak-base or weak-acid drug molecules across the plasma membrane of a tumor cell is dependent upon the acid-dissociation constant (pKa) of the drug as well as the plasmalemmal pH gradient. A large acid-outside pH gradient, such as those seen in MCF-7 xenografts, can exert a protective effect on the cell from weak-base drugs such as anthracyclines and Vinca alkaloids, which have pKa values of 7.5 to 9.5. The possibility of enhancing the therapeutic efficacy of weak-base drugs by dietary or metabolic manipulation of the extracellular pH, in order to reduce or reverse the plasmalemmal pH gradient, deserves investigation.     

断层侧向封闭性的粘土涂抹势研究方法及应用

在深入分析粘土涂抹成因及其发育影响因素的基础上，根据粘土涂抹势与断层侧向封闭性之间的对应关系，建立了一套利用粘涂抹势研究断层侧向封闭性的方法，并将春应用于松辽盆地三站气田扶余和杨大城子油层的侧向封闭性研究中，其研究结果较客观地反映了该气田内气水分布规律，表明该方法对于断层侧向封闭性的研究是可行的。     

A conjugate of ristomycin A ristosaminylaglycon-polymyxin B: the spectrum of its antimicrobial action and its membranolytic activity

Antimicrobial activity of a conjugate based on two antibiotics, i.e. ristomycin A and polymyxin B was studied. The conjugate was shown to have a broad antimicrobial spectrum. In concentrations of 5 to 30 micrograms/ml it inhibited the growth of gram-positive and gram-negative bacteria and in concentrations of 5 to 40 micrograms/ml it inhibited the growth of the pathogenic clinical strains. An insignificant membranolytic action of the conjugate with respect to membranes of the susceptible bacteria and no hemolytic action on human red blood cells were detected.     

Comments on “The Cramer-Rao lower bounds for signals withconstant amplitude and polynomial phase”

For original paper see IEEE Trans. Signal Processing, vol.39, p.749-52 (March 1991). Different expressions for the Cramer-Rao lower bounds (CRLBs) of constant amplitude polynomial phase signals embedded in white Gaussian noise appear in the literature. The present paper revisits the derivation of the bounds reported by Peleg and Porat (1991) and indicates that the resulting expressions depend on the interval over which the signal is defined. The proper choice of the interval is the one that centers the signal around zero and results in the minimum lower bounds     

Two antipeptide monoclonal antibodies that recognize adhesive sequences in fibrinogen: identification of antigenic determinants and unrelated sequences using synthetic combinatorial libraries

Fulminant hepatic failure is infrequently seen as a consequence of acute congestive heart failure. Recognition of this entity is important as treatment directed towards heart failure should help resolve the liver failure. A case of fulminant hepatic failure due to previously unrecognized cardiomyopathy is presented. A liver transplantation was being considered for fulminant hepatic failure until hemodynamic monitoring studies demonstrated that, in fact, the patient had severe cardiomyopathy. Treatment directed at his cardiomyopathy resolved the liver failure. Therefore, prompt recognition of such a phenomenon would enable early institution of appropriate therapeutic measures with the hope of clinical benefit to the patient.     

Effect of cAMP-induced transcription on the repair of the phosphoenolpyruvate carboxykinase gene by hepatocytes isolated from young and old rats

Animal experiments suggest that the fetal brain is sensitive to nicotine. Although much attention has been given to the relation between cigarette smoking during pregnancy and neurodevelopment in children, this remains controversial. Our study describes the relationship between maternal cigarette smoking during pregnancy and babbling abilities of the 8-month-old infant. In a longitudinal cohort, information was collected at the 16th week of gestation, at delivery and when the infant was about 8 months old. At this age babbling abilities of the infant were evaluated by a health visitor during a home visit. Singleton infants without any disability born at Aarhus University Hospital, Denmark, 1991-92 and still living in the Community of Aarhus at the age of 8 months were eligible (n = 2302). Complete follow-up was obtained for 1871 children (81.3%). A dose-response-like relationship between number of cigarettes smoked per day during pregnancy and babbling abilities was found after controlling for potential confounders. Smoking 10 or more cigarettes per day during pregnancy almost doubled the risk (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.1-3.6) of the infant being a non-babbler at the examination at 8 months. Among children who were breast fed for less than 4 months this risk was even higher (OR = 2.7, CI 1.3-5.8).