Arabidopsis ROOT UVB SENSITIVE2/WEAK AUXIN RESPONSE1 is required for polar auxin transport.

Auxin is an essential phytohormone that regulates many aspects of plant development. To identify new genes that function in auxin signaling, we performed a genetic screen for Arabidopsis thaliana mutants with an alteration in the expression of the auxin-responsive reporter DR5rev:GFP (for green fluorescent protein). One of the mutants recovered in this screen, called weak auxin response1 (wxr1), has a defect in auxin response and exhibits a variety of auxin-related growth defects in the root. Polar auxin transport is reduced in wxr1 seedlings, resulting in auxin accumulation in the hypocotyl and cotyledons and a reduction in auxin levels in the root apex. In addition, the levels of the PIN auxin transport proteins are reduced in the wxr1 root. We also show that WXR1 is ROOT UV-B SENSITIVE2 (RUS2), a member of the broadly conserved DUF647 domain protein family found in diverse eukaryotic organisms. Our data indicate that RUS2/WXR1 is required for auxin transport and to maintain the normal levels of PIN proteins in the root.

Complex regulation of the TIR1/AFB family of auxin receptors.

Auxin regulates most aspects of plant growth and development. The hormone is perceived by the TIR1/AFB family of F-box proteins acting in concert with the Aux/IAA transcriptional repressors. Arabidopsis plants that lack members of the TIR1/AFB family are auxin resistant and display a variety of growth defects. However, little is known about the functional differences between individual members of the family. Phylogenetic studies reveal that the TIR1/AFB proteins are conserved across land plant lineages and fall into four clades. Three of these subgroups emerged before separation of angiosperms and gymnosperms whereas the last emerged before the monocot-eudicot split. This evolutionary history suggests that the members of each clade have distinct functions. To explore this possibility in Arabidopsis, we have analyzed a range of mutant genotypes, generated promoter swap transgenic lines, and performed in vitro binding assays between individual TIR1/AFB and Aux/IAA proteins. Our results indicate that the TIR1/AFB proteins have distinct biochemical activities and that TIR1 and AFB2 are the dominant auxin receptors in the seedling root. Further, we demonstrate that TIR1, AFB2, and AFB3, but not AFB1 exhibit significant posttranscriptional regulation. The microRNA miR393 is expressed in a pattern complementary to that of the auxin receptors and appears to regulate TIR1/AFB expression. However our data suggest that this regulation is complex. Our results suggest that differences between members of the auxin receptor family may contribute to the complexity of auxin response.

Multivariate characterization of white matter heterogeneity in autism spectrum disorder.

The complexity and heterogeneity of neuroimaging findings in individuals with autism spectrum disorder has suggested that many of the underlying alterations are subtle and involve many brain regions and networks. The ability to account for multivariate brain features and identify neuroimaging measures that can be used to characterize individual variation have thus become increasingly important for interpreting and understanding the neurobiological mechanisms of autism. In the present study, we utilize the Mahalanobis distance, a multidimensional counterpart of the Euclidean distance, as an informative index to characterize individual brain variation and deviation in autism. Longitudinal diffusion tensor imaging data from 149 participants (92 diagnosed with autism spectrum disorder and 57 typically developing controls) between 3.1 and 36.83 years of age were acquired over a roughly 10-year period and used to construct the Mahalanobis distance from regional measures of white matter microstructure. Mahalanobis distances were significantly greater and more variable in the autistic individuals as compared to control participants, demonstrating increased atypicalities and variation in the group of individuals diagnosed with autism spectrum disorder. Distributions of multivariate measures were also found to provide greater discrimination and more sensitive delineation between autistic and typically developing individuals than conventional univariate measures, while also being significantly associated with observed traits of the autism group. These results help substantiate autism as a truly heterogeneous neurodevelopmental disorder, while also suggesting that collectively considering neuroimaging measures from multiple brain regions provides improved insight into the diversity of brain measures in autism that is not observed when considering the same regions separately. Distinguishing multidimensional brain relationships may thus be informative for identifying neuroimaging-based phenotypes, as well as help elucidate underlying neural mechanisms of brain variation in autism spectrum disorders.

The arabidopsis serrate gene encodes a zinc-finger protein required for normal shoot development.

Organogenesis in plants depends upon the proper regulation of many genes, but how such necessary changes in gene expression are coordinated is largely unknown. The serrate (se) mutant of Arabidopsis displays defects in the initiation and elaboration of cotyledons and post-embryonic lateral organs. Cloning the SE gene revealed that it encodes a protein with a single, C(2)H(2)-type, zinc finger related to genes in other eukaryotes. Consistent with a role in organogenesis, the SE gene is transcribed in shoot meristems and in emerging organ primordia throughout development. Expression of the SE cDNA under the control of a heterologous promoter caused both accelerated and arrested plant growth, and these phenotypes were due to overexpression and co-suppression of the SE gene, respectively. Our analysis of the se mutant and the SE gene suggests a role for the SE gene product in regulating changes in gene expression via chromatin modification. Consistent with this proposed function, a synergistic double mutant phenotype was seen for plants mutant at both the SE locus and the locus encoding the largest subunit of chromatin assembly factor I.

Association between reduced human leukocyte antigen (HLA)-DR expression on blood monocytes and increased plasma level of interleukin-10 in patients with severe burns.

Severe thermal injury causes an immune dysfunction which includes a decrease of monocyte human leukocyte antigen DR (HLA-DR) expression. Interleukin-10 exerts a negative influence on this parameter in vitro. In this study we determined the prognostic value of reduced monocyte HLA-DR expression with regard to infectious complications, and the in vivo association between monocyte HLA-DR and plasma interleukin-10 concentration. Both quantities were measured serially in 19 patients with severe burns. HLA-DR expression was determined by direct immunofluorescence on a flow cytometer, and interleukin-10 was measured by ELISA. After burn trauma the percentage of HLA-DR expressing monocytes fell markedly (median: 53% at day 2, 36% at day 4, 31% at day 7, 28% at day 9, 35% at day 12, and 42% at day 14; compared to 93% for healthy volunteers). Moreover, patients who became septic showed lower monocyte HLA-DR expression than non-septic patients; the differences were significant at day 2 (p < 0.01) and day 7 (p < 0.05). Plasma concentrations of interleukin-10 increased after thermal injury (median: 40 ng/l at day 2, 43 ng/l at day 4, 77 ng/l at day 7, 120 ng/l at day 9, 63 ng/l at day 12, and 82 ng/l at day 14). Individual HLA-DR expression and interleukin-10 concentration were negatively correlated, the association reaching statistical significance at day 4 (p=0.006) and day 7 (p=0.031). Thus, after severe burn injury monocyte HLA-DR expression has prognostic value and is negatively associated with interleukin-10 plasma concentration.

The control of trichome spacing and number in Arabidopsis.

Arabidopsis trichomes are single-celled epidermal hairs that serve as a useful model for the study of plant cell differentiation. An examination of the distribution of trichomes early in their development revealed that developing trichomes occur adjacent to another trichome much less frequently than would be expected by chance. Clonal analysis of epidermal cell lineages ruled out a role for cell lineage in generating the observed minimum-distance spacing pattern. Taken together, these results are consistent with a role for lateral inhibition in the control of trichome development. We also report the identification of a new locus, Reduced Trichome Number (RTN), which affects the initiation of trichomes. This locus was initially detected by the reduced number of leaf trichomes on Landsberg erecta plants compared to that on Columbia plants. Quantitative Trait Locus mapping revealed that more than 73% of the variation in trichome number was due to a major locus near erecta on chromosome 2. The reduced number of trichomes conditioned by the Landsberg erecta allele of this locus appeared to be due to an early cessation of trichome initiation. The implications of these observations are discussed with regard to previously published models of trichome development.

REVOLUTA regulates meristem initiation at lateral positions.

While the shoot apical meristem (SAM) is indirectly responsible for the initiation of all above-ground postembryonic organs, in most plants the vast majority of these organs are directly initiated by lateral meristems. In Arabidopsis thaliana, the lateral meristems include flower meristems (FMs), which form on the flanks of the SAM, and lateral shoot meristems (LSMs), which develop in leaf axils. While significant progress has been made on the molecular genetic basis of SAM initiation during embryo development, relatively little is known about the initiation of meristems at lateral positions. Here we have characterized the phenotypic consequences and genetic interactions of mutations in the REVOLUTA (REV) gene, with an emphasis on the role of REV in lateral meristem initiation. Our observations indicate that REV is required for initiation of both LSMs and FMs, and likely acts in the same pathway as, and upstream of, known meristem regulators. We identified the REV gene and found it encodes a predicted homeodomain/leucine zipper transcription factor that also contains a START sterol-lipid binding domain. REV is the same as the IFL gene. REV was expressed at the earliest stages of LSM and FM formation. Within the inflorescence shoot meristem, REV expression appeared to predict 3--5 incipient flower primordia on the flanks of the SAM, and REV expression at stage 1 and stage 2 matched that of WUS and STM, respectively. We propose that REV acts at lateral positions to activate the expression of known meristem regulators.