Acyclovir inhibition of IDO to decrease Tregs as a glioblastoma treatment adjunct

Regulatory T cells, Tregs, are a subset of lymphocytes that have immunosuppressive attributes. They are elevated in blood of glioblastoma patients and within this tumor's tissue itself. Indoleamine 2,3-dioxygenase, IDO, converts tryptophan to kynurenine. IDO activity enhances Treg formation by pathways that are unknown. Experimentally, inhibition of IDO decreases Treg function and number in rodents. The common anti-viral agent acyclovir inhibits IDO. Acyclovir may thereby decrease Treg function in glioblastoma. If it can be confirmed that Treg counts are elevated in glioblastoma patients' tumor tissue, and if we can document acyclovir's lowering of tissue Treg counts by a small trial of acyclovir in pre-operative glioblastoma patients, a trial of acyclovir effect on survival should be done given the current poor prognosis of glioblastoma and the well-established safety and low side effect burden of acyclovir

A morphometric analysis of Actaea racemosa L. (Ranunculaceae)

Actaea racemosa L. (syn. Cimicifuga racemosa [L.] Nutt.), Ranunculaceae, commonly known as black cohosh, is an herbaceous, perennial, medicinal plant native to the deciduous woodlands of eastern North America. Historical texts and current sales data indicate the continued popularity of this plant as an herbal remedy for over 175 years. Much of the present supply of A. racemosa is harvested from the wild. Diversity within and between populations of the species has not been well characterized. The purpose of this study was to assess the morphological variation of A. racemosa and identify patterns of variation at the population and species levels. A total of 26 populations representative of a significant portion of the natural range of the species were surveyed and plant material was collected for the morphological analysis of 37 leaflet, flower, and whole plant characteristics. In total, 511 leaflet samples and 83 flower samples were examined. Several of the populations surveyed had sets of relatively unique characteristics (large leaflet measurements, tall leaves and flowers, and a large number of stamen), and Tukey-Kramer multiple comparisons revealed significant differences between specific populations for 20 different characteristics. No unique phenotype, however, was found. Considerable morphological plasticity was noted in the apices of the staminodia. Cluster analyses showed that the morphological variation within populations was not smaller than between population and that this variation in not influenced by their geographic distribution

The in-medium isovector pi N amplitude from low energy pion scattering

Differential cross sections for elastic scattering of 21.5 MeV positive and negative pions by Si, Ca, Ni and Zr have been measured as part of a study of the pion-nucleus potential across threshold. The `anomalous' repulsion in the s-wave term was observed, as is the case with pionic atoms. The extra repulsion can be accounted for by a chiral-motivated model where the pion decay constant is modified in the medium. Unlike in pionic atoms, the anomaly cannot be removed by merely introducing an empirical on-shell energy dependence.Comment: 9 pages, 2 figures. Minor changes, to appear in PR

Elastic scattering of low energy pions by nuclei and the in-medium isovector pi N amplitude

Measurements of elastic scattering of 21.5 MeV pi+ and pi- by Si, Ca, Ni and Zr were made using a single arm magnetic spectrometer. Absolute calibration was made by parallel measurements of Coulomb scattering of muons. Parameters of a pion-nucleus optical potential were obtained from fits to all eight angular distributions put together. The `anomalous' s-wave repulsion known from pionic atoms is clearly observed and could be removed by introducing a chiral-motivated density dependence of the isovector scattering amplitude, which also greatly improved the fits to the data. The empirical energy dependence of the isoscalar amplitude also improves the fits to the data but, contrary to what is found with pionic atoms, on its own is incapable of removing the anomaly.Comment: 20 pages, 5 figures, 5 tables. V2 added details on uncertainties,extended discussion. To appear in PR

Short Communication: Simultaneous Identification of Five κ-Casein (CSN3) Alleles in Domestic Goat by Polymerase Chain Reaction-Single Strand Conformation Polymorphism

Until now, a total of nine polymorphic sites corresponding to six different alleles have been described at the kappa-casein (CSN3) locus in the domestic goat (Capra hircus). A protocol for the rapid and simultaneous genotyping of five goat CSN3 alleles by using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique was developed. Moreover, the developed test was validated by screening the CSN3 variability in four Italian breeds, Garganica, Jonica, Maltese, and Camosciata. Seven different patterns were readily identifiable. These corresponded to five known alleles and two newly identified variants. The G/A substitution at nucleotide position 471, which is not identifiable at the protein level but was found to be very frequent in the typed breeds, is easily detectable by the protocol developed. The PCR-SSCP analysis is a powerful tool for the genetic study of CSN3 variability in domestic goats, allowing both the simultaneous identification of different alleles, and the detection of new variants

Characterization of the casein gene complex in West Africa goats and description of a new αs1-casein polymorphism

The analysis of casein polymorphisms was carried out in West Africa goat populations: Red Sokoto (n = 57), West African Dwarf Nigeria (n = 27), West African Dwarf Cameroon (n = 39), and Borno (n = 37). The 4 casein genes alphas1 (CSN1S1), beta (CSN2), alphas2 (CSN1S2), and kappa (CSN3) were typed at the DNA level. No null alleles were found in any of the genes analyzed. A PCR single-strand conformation polymorphism method was implemented for the identification of CSN1S1*F allele simultaneously with A/01, B/E, N and the new allele. The allele differed from CSN1S1*B by a synonymous transversion TCG->TCT in the codon corresponding to Ser66 of the mature protein. The new allele, named CSN1S1*B', occurred at a high frequency in all the populations, ranging from 0.295 (West African Dwarf Cameroon) to 0.405 (Borno). A greater frequency was found for alleles associated with high alphas1-casein quantity, as has already been observed in the goat populations from the Mediterranean area. The intermediate E allele occurred only in the Red Sokoto and at a low frequency. The faint F allele occurred in 3 populations at frequencies lower than 0.03. Linkage disequilibrium occurred in all the populations, with highly significant differences in Borno, Red Sokoto, and West Africa Dwarf Nigeria, and significant differences in West Africa Dwarf Cameroon. Only 10 haplotypes showed frequencies >= 0.05 in at least 1 of the 4 populations considered, and the overall frequency was >0.1 only for 4 haplotypes: BAAB, B'ACA, ACAB, and BACA (in the order CSN1S1-CSN2-CSN1S2-CSN3). Haplotype BAAB, postulated as an ancestral haplotype in previous studies, was the most common haplotype in all breeds except Borno, where B'ACA was predominant. The results obtained are of considerable significance given that very little information exists on the subject for African goats. The high frequency of strong alleles in the calcium-sensitive caseins as well as the high linkage disequilibrium found among the casein genes in the African breeds analyzed may suggest that specific casein haplotypes have already been selected due to their advantages for nutrition. Haplotypes providing greater protein and casein content would increase the energy content of milk, thus resulting in more favorable growth and survival of young goats and humans consuming the milk