Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/− Mouse, a Model of Cornelia de Lange Syndrome

Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75–80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only ∼30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl+/− mice and in individuals with CdLS

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Visual imagery is not always like visual perception

The Perky effect is the interference of visual imagery with vision. Studies of this effect show that visual imagery has more than symbolic properties, but these properties differ both spatially (including pictorially ) and temporally from those of vision. We therefore reject both the literal picture-in-the-head view and the entirely symbolic view

Illusory illusory conjunctions: The conjoining of features of visual and imagined stimuli

The question of whether illusory conjunctions would occur with visual mental imagery was investigated. In 4 experiments, participants were tachistoscopically presented displays of geometrical figures (varying in shape, color, and solidity) flanked by 2 digits. For half of the trials, participants imagined one of the figures in the display. Illusory conjunctions occurred between the features of the physical (cued) and imagined figures, which suggests that imagery influences perception at the level of visual processing at which features are combined. Moreover, the conjunction errors induced by an imagined figure were similar to those induced by a physical figure with the same features. The pattern of errors could not be accounted for by guessing. Together, these findings support the view that there can be correspondence between visual imagery and visual perception

Effects of Imagery on Vernier Acuity under Conditions of Induced Depth

Imagery interferes with visual acuity (the Perky effect ) when an image is close to a visual target and both the image and the acuity target are located in the same depth plane. Whether imagery-induced interference occurs when a mental image and a target are separated by induced depth was investigated. Participants projected an image in front of or behind a vernier acuity target on a frontal or back plane suggested by the panels of an outline cube. A drop in accuracy for the target was found when an image was projected in front of, but not behind, the target. Thus, induced depth can influence the Perky effect. By contrast, real lines interfered with the target regardless of perceived depth plane, which is inconsistent with the hypothesis that imagery and perception are equivalent. Results support the hypothesis that images interfere with perception only when the participant must see through an image to obtain information specifying the visual target

Early onset of pre-lethal effects of lotilaner (Credelio®) on Amblyomma americanum ticks on experimentally infested dogs

Abstract Background The speed with which acaricides paralyze and kill ticks is relevant to impeding pathogen transmission. The objective of this study was to assess early-onset lotilaner effects on the motility and weights of Amblyomma americanum ticks collected from treated dogs. Methods Twelve healthy dogs were randomized between two groups to receive either lotilaner (Credelio®) on Day 0 or to be sham treated. On Day 7, 25 male and 25 female A. americanum were placed under bandages, two on each flank of each dog. After 30 or 45 min, all unattached ticks were removed and T = 0 was set. At T = 2, 4, 8 and 24 h post attachment, 5 attached ticks removed from each bandage on each dog were weighed, assessed by blinded observers for righting ability and movement recorded. Results After the infestation period significantly fewer treated than control dogs had 20 ticks attached (50.0% versus 91.7%, P = 0.0015). At 24 h post attachment, mean weights of ticks from treated dogs (males 1.69 mg; females 2.72) were significantly less than ticks from controls (males 2.66 mg; females 4.67) (P male = 0.0002; P female < 0.0001). Mean tick weights from the treated group were significantly lower at 24 h than at earlier time points (P male < 0.0307; P female = 0.0021). At 4 and 8 h, significantly fewer ticks from treated (14.3%, 0.0%, respectively) than from control dogs could right (73.3%, 70.0%) (P 4h < 0.0001; P 8h = 0.0024) (at 24 h, all ticks from treated dogs were dead), and distance moved was significantly less at all time points (P 2h = 0.0413; P 4h, P 8h < 0.0001). Mean and maximum velocity of ticks from treated dogs were significantly lower, relative to controls, at 4 and 8 h (P ≤ 0.0001). Within the treated group, collected ticks had significantly lower mean and maximum velocities at 4 and 8 h compared to 2 h (P mean < 0.0042; P max < 0.0194). Conclusion The observed changes indicate that lotilaner may disrupt tick attachment. In ticks that attached, a progressive impairment of neuromuscular processes began within 2 h. Those irreversible changes could substantially reduce the risk of pathogen transmission from tick to host