Dominant Mutations in KAT6A Cause Intellectual Disability with Recognizable Syndromic Features

Through a multi-center collaboration study, we here report six individuals from five unrelated families, with mutations in KAT6A/MOZ detected by whole-exome sequencing. All five different de novo heterozygous truncating mutations were located in the C-terminal transactivation domain of KAT6A: {"type":"entrez-nucleotide","attrs":{"text":"NM_001099412.1","term_id":"150378462","term_text":"NM_001099412.1"}}NM_001099412.1: c.3116_3117 delCT, p.(Ser1039^∗); c.3830_3831insTT, p.(Arg1278Serfs^∗17); c.3879 dupA, p.(Glu1294Argfs^∗19); c.4108G>T p.(Glu1370^∗) and c.4292 dupT, p.(Leu1431Phefs^∗8). An additional subject with a 0.23 MB microdeletion including the entire KAT6A reading frame was identified with genome-wide array comparative genomic hybridization. Finally, by detailed clinical characterization we provide evidence that heterozygous mutations in KAT6A cause a distinct intellectual disability syndrome. The common phenotype includes hypotonia, intellectual disability, early feeding and oromotor difficulties, microcephaly and/or craniosynostosis, and cardiac defects in combination with subtle facial features such as bitemporal narrowing, broad nasal tip, thin upper lip, posteriorly rotated or low-set ears, and microretrognathia. The identification of human subjects complements previous work from mice and zebrafish where knockouts of Kat6a/kat6a lead to developmental defects.     

Seasonal occurrence of key arthropod pests and associated natural enemies in Alabama Satsuma citrus

Six Alabama Satsuma mandarin orchards (four conventionally sprayed and two unsprayed) were surveyed during 2005 and 2006 to determine the population dynamics of arthropod pests and their natural enemies. Twenty-eight arthropod pest species were encountered; the major foliage pests were citrus whitefly, Dialeurodes citri (Ashmead); purple scale, Lepidosaphes beckii (Newman); Glover scale, L. gloveri (Packard); and citrus red mite, Panonychus citri (McGregor). Two distinct population peaks were recorded for citrus whitefly at most locations. The most important direct sources of citrus whitefly mortality were parasitism by Encarsia lahorensis (Howard) and infection by the pathogenic fungus, Aschersonia aleyrodis Webber. In general, all stages of both scale insects (purple scale and Glover scale) were present in the orchards year-round, indicative of overlapping generations; however, the highest densities were recorded during the early season. Citrus whitefly, purple scale, and Glover scale were more abundant on leaves collected from the interior of the tree canopy than in the exterior canopy. Citrus red mite densities were highest in the spring, with populations declining at the start of the summer, and were more abundant in the exterior canopy than in the interior canopy. The most important natural enemies of citrus red mite were predatory mites belonging to several families, of which Typhlodromalus peregrinus Muma (Phytoseiidae) was the predominant species. Major differences were recorded in the relative abundance of different arthropod pest species in the orchards: citrus whitefly, purple scale, and Glover scale predominated in the unsprayed orchards, whereas citrus red mite infestations were more severe in the sprayed orchards. The results are discussed in relation to the possible effect of orchard management practices on abundance of the major pests.     

Arizonasaurus and its implications for archosaur divergence

The Moenkopi Formation has yielded partial and isolated remains of important archosaurs including rauisuchian skull fragments and isolated poposaur centra and pelvic girdle elements. A recently discovered skeleton referable to Arizonasaurus babbitti shows that most of these archosaurian remains belong to one taxon. Characteristics of the skeleton of Arizonasaurus show that it belongs to a poorly known group of Middle Triassic (240-230 Myr ago) archosaurs called the ctenosauriscids, and that ctenosauriscids are or are closely related to poposaurs. Furthermore, many characteristics of Arizonasaurus provide evidence that poposaurids and ctenosauriscids are derived rauisuchians. The presence of a poposaurid in the early Middle Triassic suggests that the divergence of birds and crocodiles occurred earlier than previously thought. Middle Triassic ctenosauriscids also allow the correlation of Triassic faunas in Europe, Asia, North America and Africa. The Moenkopi Formation fauna represents a transitional fauna between Early and Late Triassic faunas.     

New technologies in scanning probe microscopy for studying molecular interactions in cells

Atomic force microscopy (AFM) is a specialised form of scanning probe microscopy, which was invented by Binnig and colleagues in 1986. Since then, AFM has been increasingly used to study biomedical problems. Because of its high resolution, AFM has been used to examine the topography or shape of surfaces, such as during the molecular imaging of proteins. This, combined with the ability to operate under known force regimes, makes AFM technology particularly useful for measuring intermolecular bond forces and assessing the mechanical properties of biological materials. Many of the constraints (e.g. complex instrumentation, slow acquisition speeds and poor vertical range) that previously limited the use of AFM in cell biology are now beginning to be resolved. Technological advances will enable AFM to challenge both confocal laser scanning microscopy and scanning electron microscopy as a method for carrying out three-dimensional imaging. Its use as both a precise micro-manipulator and a measurement tool will probably result in many novel and exciting applications in the future. In this article, we have reviewed some of the current biological applications of AFM, and illustrated these applications using studies of the cell biology of bone and integrin-mediated adhesion.     

Metal ion dependence, thermodynamics, and kinetics for intramolecular docking of a GAAA tetraloop and receptor connected by a flexible linker

The GAAA tetraloop-receptor motif is a commonly occurring tertiary interaction in RNA. This motif usually occurs in combination with other tertiary interactions in complex RNA structures. Thus, it is difficult to measure directly the contribution that a single GAAA tetraloop-receptor interaction makes to the folding properties of a RNA. To investigate the kinetics and thermodynamics for the isolated interaction, a GAAA tetraloop domain and receptor domain were connected by a single-stranded A(7) linker. Fluorescence resonance energy transfer (FRET) experiments were used to probe intramolecular docking of the GAAA tetraloop and receptor. Docking was induced using a variety of metal ions, where the charge of the ion was the most important factor in determining the concentration of the ion required to promote docking {[Co(NH(3))(6)(3+)] < [Ca(2+)], [Mg(2+)], [Mn(2+)] < [Na(+)], [K(+)]}. Analysis of metal ion cooperativity yielded Hill coefficients of approximately 2 for Na(+)- or K(+)-dependent docking versus approximately 1 for the divalent ions and Co(NH(3))(6)(3+). Ensemble stopped-flow FRET kinetic measurements yielded an apparent activation energy of 12.7 kcal/mol for GAAA tetraloop-receptor docking. RNA constructs with U(7) and A(14) single-stranded linkers were investigated by single-molecule and ensemble FRET techniques to determine how linker length and composition affect docking. These studies showed that the single-stranded region functions primarily as a flexible tether. Inhibition of docking by oligonucleotides complementary to the linker was also investigated. The influence of flexible versus rigid linkers on GAAA tetraloop-receptor docking is discussed.     

Invasive species cause large-scale loss of native California oyster habitat by disrupting trophic cascades

Although invasive species often resemble their native counterparts, differences in their foraging and anti-predator strategies may disrupt native food webs. In a California estuary, we showed that regions dominated by native crabs and native whelks have low mortality of native oysters (the basal prey), while regions dominated by invasive crabs and invasive whelks have high oyster mortality and are consequently losing a biologically diverse habitat. Using field experiments, we demonstrated that the invasive whelk’s distribution is causally related to a large-scale pattern of oyster mortality. To determine whether predator–prey interactions between crabs (top predators) and whelks (intermediate consumers) indirectly control the pattern of oyster mortality, we manipulated the presence and invasion status of the intermediate and top trophic levels in laboratory mesocosms. Our results show that native crabs indirectly maintain a portion of the estuary’s oyster habitat by both consuming native whelks (density-mediated trophic cascade) and altering their foraging behavior (trait-mediated trophic cascade). In contrast, invasive whelks are naive to crab predators and fail to avoid them, thereby inhibiting trait-mediated cascades and their invasion into areas with native crabs. Similarly, when native crabs are replaced with invasive crabs, the naive foraging strategy and smaller size of invasive crabs prevents them from efficiently consuming adult whelks, thereby inhibiting strong density-mediated cascades. Thus, while trophic cascades allow native crabs, whelks, and oysters to locally co-exist, the replacement of native crabs and whelks by functionally similar invasive species results in severe depletion of native oysters. As coastal systems become increasingly invaded, the mismatch of evolutionarily based strategies among predators and prey may lead to further losses of critical habitat that support marine biodiversity and ecosystem function. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.