CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1:15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci. Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.     

Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ～10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.     

Mixtures of Autoregressions with an Improper Component for Panel Data

An EM algorithm for fitting mixtures of autoregressions of low order is constructed and the properties of the estimators are explored on simulated and real datasets. The mixture model incorporates a component with an improper density, which is intended for outliers. The model is proposed as an alternative to the search for the order of a single-component autoregression. The methods can be adapted to other patterns of dependence in panel data. An application to the monthly records of income of the outlets of a retail company is presented.     

Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome

We identified de novo truncating mutations in ARID1B in three individuals with Coffin-Siris syndrome (CSS) by exome sequencing. Array-based copy-number variation (CNV) analysis in 2,000 individuals with intellectual disability revealed deletions encompassing ARID1B in 3 subjects with phenotypes partially overlapping that of CSS. Taken together with published data, these results indicate that haploinsufficiency of the ARID1B gene, which encodes an epigenetic modifier of chromatin structure, is an important cause of CSS and is potentially a common cause of intellectual disability and speech impairment.     

Exotic plants in early and late seral vegetation of fifteen northern Rocky Mountain environments (HTs)

We determined the capacity of exotic plants to invade major environmental types of the northern Rocky Mountains. We did this by observing their presence on disturbed and undisturbed sites in relatively well inoculated locations--corridors adjacent to highways--on transects across the mountains in Glacier National Park and Grand Teton National Park and on low-altitude sites between them. We draw 3 primary conclusions. First, of 29 exotics commonly found, the most dominant are intentionally introduced grasses ( Agrostis, Bromus, Dactylis , and especially Phleum pratense and Poa pratensis ) and legumes ( Melilotus, Medicago , and Trifolium ) rather than the forbs more often listed as noxious. Second, in the environmental types studied, disturbed sites are invasible, except in the alpine. Third, invasion of undisturbed sites declines from grasslands and open forests to alpine to moist forests. This gradient probably represents a decline in resource (light, water, nutrients) availability for herbs, except in the alpine, where a physical limitation is suggested by the poor performance of exotics on noncompetitive disturbed sites.     

Temperature-related behavior of some migrant birds in the desert

Behavior of migrant birds in relation to temperature was studied and compared to that of resident species in the northern Mojave Desert. Migrants reduced foraging intensity above 30 C, but resident species showed no striking decrease in intensity of foraging at temperatures up to 35 C. Migrant species shifted activities to shaded microhabitats at temperatures between 20 and 30 C; the resident Verdin showed a similar shift at 35 C. Most migrants decreased the amount of time spent foraging at temperatures above 30; Verdins showed a similar but stronger response to temperatures about 30 C. Significant reductions in the use of hovering and hawking maneuvers were found among migrants at temperatures above 30 C. Migrants showed similar types of behavioral adjustments to temperatures as did resident desert species, but they responded earlier in the daily temperature cycle. Desert birds appear to correlate their daily activity strongly with temperature, but nondesert species may respond either to temperature or time of day.     

Microvelia rasilis Drake in Arizona: a species new to the United States (Heteroptera: Veliidae)

Microvelia rasilis Drake was taken in Montezuma Well, Yavapai Co., Arizona, along with Microvelia hinei Drake and Hydrometra aemula Drake (Heteroptera: Hydrometridae). These are all new to this locality; however, the latter two species are previously known from Arizona.     

Arthropod and plant communities as indicators of land rehabilitation effectiveness in a semiarid shrubsteppe

We describe a case study evaluating the ecological impact of Bromus tectorum L. (cheatgrass) invasion following fire disturbance and the effectiveness of revegetation as a means of rehabilitation in a degraded semiarid shrubsteppe system. The effectiveness of rehabilitation efforts was assessed relative to arthropod richness, vegetation and arthropod community composition, and ground-cover characteristics in 3 habitats: undisturbed, burned and weed infested ( B. tectorum ), and burned then rehabilitated with native and nonnative vegetation. Arthropods were collected in each habitat using pitfall traps. Differences in arthropod richness were compared using rarefaction curves. Nonmetric multidimensional scaling and nonparametric multivariate statistical procedures, including analysis of similarity and similarity percentage routines, were used to compare arthropod and vegetation community composition and ground-cover characteristics between habitats. Arthropod communities in the rehabilitated habitat were distinct from those observed in the undisturbed and weed-infested habitats. Rehabilitation in this study resulted in a shift toward conditions observed in an undisturbed habitat and perhaps is an intermediate step to complete restoration. Arthropod richness, arthropod and vegetation community composition, and ground-cover characteristics were all useful indicators but returned slightly different results. Assessing multiple variables yielded the most complete understanding of the habitats studied.     

Effect of Timing of Grazing on Soil-Surface Crytogamic Communities in a Great Basin Low-Shrub Desert: A Preliminary Report

Cover and species richness of vascular and cryptogamic components of the plant community were inventoried in experimental grazing paddocks at the USDA/FS Desert Range Experimental Station, Millard County, Utah. The grazing treatments considered have been applied continuously for over 50 years. The effects of heavy (ca 17 sheep days/acre) grazing treatment applied in two different seasons (early winter versus a split between early and late winter) differed significantly between seasons. Cryptogamic cover and cryptogamic species richness both showed larger decreases under early-late as opposed to early winter only grazing. Vascular plant cover (relative to controls) was also reduced by early-late winter grazing, but not to a significant degree. Late season grazing, likewise, had no significant effect on number of vascular species per transect.