The Arabidopsis tandem zinc finger protein AtTZF1 affects ABA- and GA-mediated growth, stress and gene expression responses

Tandem zinc finger (TZF) proteins are characterized by two zinc-binding CCCH motifs arranged in tandem. Human TZFs such as tristetraproline (TTP) bind to and trigger the degradation of mRNAs encoding cytokines and various regulators. Although the molecular functions of plant TZFs are unknown, recent genetic studies have revealed roles in hormone-mediated growth and environmental responses, as well as in the regulation of gene expression. Here we show that expression of AtTZF1 (AtCTH/AtC3H23) mRNA is repressed by a hexokinase-dependent sugar signaling pathway. However, AtTZF1 acts as a positive regulator of ABA/sugar responses and a negative regulator of GA responses, at least in part by modulating gene expression. RNAi of AtTZF1-3 caused early germination and slightly stress-sensitive phenotypes, whereas plants over-expressing AtTZF1 were compact, late flowering and stress-tolerant. The developmental phenotypes of plants over-expressing AtTZF1 were only partially rescued by exogenous application of GA, implying a reduction in the GA response or defects in other mechanisms. Likewise, the enhanced cold and drought tolerance of plants over-expressing AtTZF1 were not associated with increased ABA accumulation, suggesting that it is mainly ABA responses that are affected. Consistent with this notion, microarray analysis showed that over-expression of AtTZF1 mimics the effects of ABA or GA deficiency on gene expression. Notably, a gene network centered on a GA-inducible and ABA/sugar-repressible putative peptide hormone encoded by GASA6 was severely repressed by AtTZF1 over-expression. Hence AtTZF1 may serve as a regulator connecting sugar, ABA, GA and peptide hormone responses.     

Actin-myosin network reorganization breaks symmetry at the cell rear to spontaneously initiate polarized cell motility

We have analyzed the spontaneous symmetry breaking and initiation of actin-based motility in keratocytes (fish epithelial cells). In stationary keratocytes, the actin network flow was inwards and radially symmetric. Immediately before motility initiation, the actin network flow increased at the prospective cell rear and reoriented in the perinuclear region, aligning with the prospective axis of movement. Changes in actin network flow at the cell front were detectable only after cell polarization. Inhibition of myosin II or Rho kinase disrupted actin network organization and flow in the perinuclear region and decreased the motility initiation frequency, whereas increasing myosin II activity with calyculin A increased the motility initiation frequency. Local stimulation of myosin activity in stationary cells by the local application of calyculin A induced directed motility initiation away from the site of stimulation. Together, these results indicate that large-scale actin-myosin network reorganization and contractility at the cell rear initiate spontaneous symmetry breaking and polarized motility of keratocytes.     

Testing concordance of clinical characteristics in familial studies with application to inflammatory bowel diseases

The etiology of chronic Inflammatory Bowel Diseases (IBD) remains unknown, with both genetic and environmental risk factors having been implicated. A recent collaborative study of IBD provides clinical data from families with three or more affected first-degree relatives. The scientific question is whether specific clinical characteristics aggregate among affected individuals within families. Gastroenterological researchers have examined the number of concordant familial pairs in familial aggregation studies, but methods and results have been discrepant. This article investigates concepts of concordance and gives a comprehensive statistical treatment for testing concordance of various clinical traits in familial studies. For dichotomous traits, the distribution of this statistic under the null hypothesis of no familial aggregation is obtained by three methods: asymptotic, probability generating function, and permutation. The permutation method is extended to analyze aggregation for non-dichotomous traits and co-aggregations between two traits. We apply the permutation method to analyze the aforementioned multiply-affected IBD family data. Evidence is found for familial clustering of various traits, some of which are not revealed in existing studies. Such analyses provide a basis for investigating the dependence of trait aggregation upon genetic or environmental risk factors.     

A de novo reciprocal t(2;18) translocation with regular trisomy 21

A 4-year-old girl with Down syndrome exhibited an autosomal translocation t(2;18) in addition to trisomy 21. An evaluation of GTG-banded metaphases revealed the karyotype 47,XX,t(2;18),21 that was confirmed by using fluorescent in situ hybridization (FISH) probes. This case represents a very rare coincidence of an autosomal aneuploidy and a structural rearrangement. Her parents showed a normal chromosome complement. The translocation must have been an apparently "balanced" one as the proband presented with typical features of Down syndrome alone. The mechanism of origin of this rearrangement along with a nondisjunctional error and its significance are discussed.     

Computational simulations of flow dynamics and blood damage through a bileaflet mechanical heart valve scaled to pediatric size and flow

Despite pressing needs, there are currently no FDA approved prosthetic valves available for use in the pediatric population. This study is performed for predictive assessment of blood damage in bileaflet mechanical heart valves (BMHVs) with pediatric sizing and flow conditions. A model of an adult-sized 23 mm St. Jude Medical (SJM) Regent^™ valve is selected for use in simulations, which is scaled in size for a 5-year old child and 6-month old infant. A previously validated lattice-Boltzmann method (LBM) is used to simulate pulsatile flow with thousands of suspended platelets for cases of adult, child, and infant BMHV flows. Adult BMHV flows demonstrate more disorganized small-scale flow features, but pediatric flows are associated with higher fluid shear stresses. Platelet damage in the pediatric cases is higher than in adult flow, highlighting thrombus complication dangers of pediatric BMHV flows. This does not necessarily suggest clinically important differences in thromboembolic potential. Highly damaged platelets in pediatric flows are primarily found far downstream of the valve, as there is less flow recirculation in pediatric flows. In addition, damage levels are well below expected thresholds for platelet activation. The extent of differences here documented between the pediatric and adult cases is of concern, demanding particular attention when pediatric valves are designed and manufactured. However, the differences between the pediatric and adult cases are not such that development of pediatric sized valves is untenable. This study may push for eventual approval of prosthetic valves resized for the pediatric population. Further studies will be necessary to determine the validity and potential thrombotic and clinical implications of these findings.     

The linked conservation of structure and function in a family of high diversity: the monomeric cupredoxins

The monomeric cupredoxins are a highly divergent family of copper binding electron transport proteins that function in photosynthesis and respiration. To determine how function and structure are conserved in the context of large sequence differences, we have carried out a detailed analysis of the cupredoxins of known structure and their sequence homologs. The common structure of the cupredoxins is formed by a sandwich of two beta sheets which support a copper binding site. The structure of the deeply buried core is intimately coupled to the binding site on the surface of the protein; in each protein the conserved regions form one continuous substructure that extends from the surface active site and through the center of the molecule. Residues around the active site are conserved for functional reasons, while those deeper in the structure will be conserved for structural reasons. Together the two sets support each other.     

Competing sound sources reveal spatial effects in cortical processing

Why is spatial tuning in auditory cortex weak, even though location is important to object recognition in natural settings? This question continues to vex neuroscientists focused on linking physiological results to auditory perception. Here we show that the spatial locations of simultaneous, competing sound sources dramatically influence how well neural spike trains recorded from the zebra finch field L (an analog of mammalian primary auditory cortex) encode source identity. We find that the location of a birdsong played in quiet has little effect on the fidelity of the neural encoding of the song. However, when the song is presented along with a masker, spatial effects are pronounced. For each spatial configuration, a subset of neurons encodes song identity more robustly than others. As a result, competing sources from different locations dominate responses of different neural subpopulations, helping to separate neural responses into independent representations. These results help elucidate how cortical processing exploits spatial information to provide a substrate for selective spatial auditory attention.