Nucleolar localization of GLTSCR2/PICT-1 is mediated by multiple unique nucleolar localization sequences

The human glioma tumor suppressor candidate region 2 gene product, GLTSCR2, also called 'protein interacting with carboxyl terminus 1' (PICT-1), has been implicated in the regulation of two major tumor suppressor proteins, PTEN and p53, and reported to bind the membrane-cytoskeleton regulator of cell signaling, Merlin. PICT-1 is a nucleolar protein, conserved among eukaryotes, and its yeast homolog has been functionally associated with ribosomal RNA processing. By means of confocal microscopy of EGFP and myc-tagged PICT-1 fusion proteins, we delineate that the nucleolar localization of PICT-1 is mediated by two independent nucleolar localization sequences (NoLS). Unlike most NoLSs, these NoLSs are relatively long with flexible boundaries and contain arginine and leucine clusters. In addition, we show that PICT-1 exhibits a nucleolar distribution similar to proteins involved in ribosomal RNA processing, yet does not colocalize precisely with either UBF1 or Fibrillarin under normal or stressed conditions. Identification of the precise location of PICT-1 and the signals that mediate its nucleolar localization is an important step towards advancing our understanding of the demonstrated influence of this protein on cell fate and tumorigenesis.     

The interface of protein structure, protein biophysics, and molecular evolution

Abstract The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction.     

Demographic and ecogeographic factors limit wild grapevine spread at the southern edge of its distribution range

The spatial distribution of plants is constrained by demographic and ecogeographic factors that determine the range and abundance of the species. Wild grapevine (Vitis vinifera ssp. sylvestris) is distributed from Switzerland in the north to Israel in the south. However, little is known about the ecogeographic constraints of this species and its genetic and phenotypic characteristics, especially at the southern edge of its distribution range in the Levant region. In this study, we explore the population structure of southern Levantine wild grapevines and the correlation between demographic and ecogeographic characteristics. Based on our genetic analysis, the wild grapevine populations in this region can be divided into two major subgroups in accordance with a multivariate spatial and ecogeographical clustering model. The identified subpopulations also differ in morphological traits, mainly leaf hairiness which may imply adaptation to environmental stress. The findings suggest that the Upper Jordan River population was spread to the Sea of Galilee area and that a third smaller subpopulation at the south of the Golan Heights may represent a distinguished gene pool or a recent establishment of a new population. A spatial distribution model indicated that distance to water sources, Normalized difference vegetation index, and precipitation are the main environmental factors constraining V. v. sylvestris distribution at its southern distribution range. These factors in addition to limited gene flow between populations prevent further spread of wild grapevines southwards to semi‐arid regions.     

Ruptured uterus in pregnancy: a Canadian hospital's experience.

Between 1966 and 1985, 15 cases of complete rupture of the uterus in pregnancy were identified among 52,854 deliveries at Foothills Provincial General Hospital, Calgary, for an incidence rate of 0.3 per 1000 deliveries. Previous cesarean section (in seven patients) was not the only predisposing factor: a history of dilatation and curettage (in two patients) or laparoscopy (in one) were also implicated. Long, obstructed labour did not appear to be a factor. Rupture also occurred in patients at low risk. The most frequent immediate complication was hypotension, in five patients. The rupture site was repaired in 11 of the patients; the other 4 underwent hysterectomy. Close surveillance and prompt intervention are the keys to good fetal and maternal outcome.