Hypothermic effects on action potential and force production of hedgehog and guinea pig papillary muscles

Action potentials and isometric force were recorded in papillary muscles from guinea pigs and summer hedgehogs at different temperatures between 37 and 0 degrees C. The action potential of the hedgehog was of a lower amplitude (mean 83 +/- 6 mV) than that of the guinea pig (mean 110 +/- 5 mV). The action potential duration at 50% repolarization was 22 +/- 2 msec in the hedgehog as compared to 105 +/- 11 msec in the guinea pig. Moreover, there was no distinct plateau phase of the hedgehog action potential. Lowering temperature prolonged the action potential duration in the two preparations by about the same percentage. However, the guinea pig preparation became progressively less excitable below 20 degrees C. Lowered temperature produced a positive inotropic effect in the guinea pig, whereas this effect was very slight in the hedgehog heart. Postextrasystolic potentiation was seen in the guinea pig but not in the hedgehog preparation. It is suggested that this difference between the preparations may be due to a greater relative amount of activator calcium in the hedgehog heart. The difference in cold tolerance between the preparations may reflect a difference in chemical composition of the sarcolemma.     

Multiple origins for phenylketonuria in Europe

Phenylketonuria (PKU), a disorder of amino acid metabolism prevalent among Caucasians and other ethnic groups, is caused primarily by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). PKU is a highly heterogeneous disorder, with more than 60 molecular lesions identified in the PAH gene. The haplotype associations, relative frequencies, and distributions of five prevalent PAH mutations (R158Q, R261Q, IVS10nt546, R408W, and IVS12n1) were established in a comprehensive European sample population and subsequently were examined to determine the potential roles of several genetic mechanisms in explaining the present distribution of the major PKU alleles. Each of these five mutations was strongly associated with only one of the more than 70 chromosomal haplotypes defined by eight RFLPs in or near the PAH gene. These findings suggest that each of these mutations arose through a single founding event that occurred within time periods ranging from several hundred to several thousand years ago. From the significant differences observed in the relative frequencies and distributions of these five alleles throughout Europe, four of these putative founding events could be localized to specific ethnic subgroups. Together, these data suggest that there were multiple, geographically and ethnically distinct origins for PKU within the European population.     

Homozygotes for the autosomal dominant neoplasia syndrome (MEN1).

Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, we had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development.     

Comparison of phospho- and dephospho-ATP citrate lyase

The dephospho- form of rat liver citrate lyase has been prepared by treating purified [³²P]-ATP citrate lyase with a partially purified phosphatase. A comparison of the properties of the phospho- and dephosphoenzyme has been performed. The pH optima were the same for both forms of the enzyme in four different buffer systems although the optimum values varied identically for both enzyme forms with the buffer. Both the phospho- and dephosphoenzymes show the same kinetic properties except for the K_m observed for ATP in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer system where it was 54 μm for the phosphoenzyme and 292 μm for the dephosphoenzyme. The present study also indicates that both enzymes are cleaved by trypsin and lysosomal proteases in a similar manner. Both forms of the enzyme tend to associate with mitochondria to the same extent and both enzymes have identical temperature stability curves.     

Group C rotavirus requires sialic acid for erythrocyte and cell receptor binding.

Current immunological and biochemical information regarding the hemagglutinin and virus-cell interactions of rotavirus is obtained exclusively from studies with group A rotaviruses. In this study, I report that the immunologically and genetically distinct group C rotavirus also possesses a hemagglutinin. The viral hemagglutinin was identified on a cultivable porcine group C rotavirus strain (strain AmC-1) by using agglutinated human and guinea pig erythrocytes. Neuraminidase treatment of fresh human erythrocytes or blocking with glycophorin A or fetuin prevented hemagglutination. Infection of swine testicular cells with group C AmC-1 virus was also prevented by glycophorin A, fetuin, and neuraminidase treatment, suggesting that sialic acid constitutes an essential part of the cell receptor.     

T cell stimulation remodels the latently HIV-1 infected cell population by differential activation of proviral chromatin

The reservoir of latently HIV-1 infected cells is heterogeneous. To achieve an HIV-1 cure, the reservoir of activatable proviruses must be eliminated while permanently silenced proviruses may be tolerated. We have developed a method to assess the proviral nuclear microenvironment in single cells. In latently HIV-1 infected cells, a zinc finger protein tethered to the HIV-1 promoter produced a fluorescent signal as a protein of interest came in its proximity, such as the viral transactivator Tat when recruited to the nascent RNA. Tat is essential for viral replication. In these cells we assessed the proviral activation and chromatin composition. By linking Tat recruitment to proviral activity, we dissected the mechanisms of HIV-1 latency reversal and the consequences of HIV-1 production. A pulse of promoter-associated Tat was identified that contrasted to the continuous production of viral proteins. As expected, promoter H3K4me3 led to substantial expression of the provirus following T cell stimulation. However, the activation-induced cell cycle arrest and death led to a surviving cell fraction with proviruses encapsulated in repressive chromatin. Further, this cellular model was used to reveal mechanisms of action of small molecules. In a proof-of-concept study we determined the effect of modifying enhancer chromatin on HIV-1 latency reversal. Only proviruses resembling active enhancers, associated with H3K4me1 and H3K27ac and subsequentially recognized by BRD4, efficiently recruited Tat upon cell stimulation. Tat-independent HIV-1 latency reversal of unknown significance still occurred. We present a method for single cell assessment of the microenvironment of the latent HIV-1 proviruses, used here to reveal how T cell stimulation modulates the proviral activity and how the subsequent fate of the infected cell depends on the chromatin context.     

金缕梅科银缕梅属与帕罗堤属的亲缘关系——核糖体DNA ITS序列证据

本文对金缕梅科弗特吉族(Molinadendron和Matudaea除外)的细胞核核糖体DNA ITS片段进行了序列分析,在此基础上对该族的演化关系、尤其是中国特有属银缕梅属的系统位置进行了最简约分支分析。基本结果如下：其一,蚊母族和狭义的弗特吉族均不形成自己的单系分支,因此,支持Endress的处理,即合并两族为广义的弗特吉族;其二,银缕梅属同帕罗堤属有着密切的亲缘关系,支持形态学和解剖学结论;其三,根据该片段核苷酸序列的演化速率推算出的银缕梅属和帕罗堤属间分化时间为晚中新世。此结论大致与化石记录相符。     

Dietary soya lecithin decreases plasma triglyceride levels and inhibits collagen- and ADP-induced platelet aggregation

Elevated plasma lipid concentrations and increased platelet activation are risk factors in the development of atherosclerosis. Nine patients with type IIa hyperlipoproteinemia and nine patients with type IV hyperlipoproteinemia were given soya lecithin, 12 g/day, for 3 months. Plasma cholesterol and triglycerides were reduced by 15 and 23%, respectively, and HDL-cholesterol increased by 16% in the hypercholesterolemic patients. Platelet function was unchanged. In the hypertriglyceridemic patients, total cholesterol fell by 18%, triglycerides by 36%, and HDL-cholesterol increased by 14%. There was a 27% reduction in platelet aggregation (P less than 0.01). Seventeen hypertriglyceridemic patients then received increasing doses of soya lecithin for 1-month periods (6, 12, and 18 g/day). The optimal lipoprotein-lowering effect was achieved with a daily dose of 12 g soya lecithin per day. Both low-density lipoprotein and very-low-density lipoprotein levels were reduced, and HDL-cholesterol and apolipoprotein levels were reduced, and HDL-cholesterol and apolipoprotein A-I concentrations were increased. Platelet aggregation in response to collagen and ADP was significantly reduced, parallel with the reduction in triglyceride level. Soya lecithin supplementing the diet may be useful in the management of the hypertriglyceridemic patient.