Self-perception of self-regulatory skills in children with attention-deficit/hyperactivity disorder aged 8–10 years

Several studies have reported a characteristic "positive illusory bias" in the self-evaluation of children with ADHD. However, results are controversial. The aim of the present study was to investigate whether children with ADHD aged 8 to 10 years can rate their self-regulatory skills accurately when assessed with an age appropriate instrument. Twenty-seven children with ADHD and 27 matched normal control children completed the Self-rating Scale of Self-regulatory Function (SelfReg), a new rating scale that has been specifically designed for this age group. As expected, children with ADHD rated themselves significantly more dysfunctional than control children. In most domains, self-ratings of children with ADHD did not diverge from parent and teacher ratings to a greater extent than self-ratings of control children, although overall results indicated a moderate tendency toward a positive bias. When a cluster analysis based on discrepancies between children's and adults' evaluations was carried out, three groups with different self-rating patterns emerged: A "positive bias" group containing exclusively children with ADHD, a "negative bias" group containing both children with ADHD and control children, and the largest group of accurate self-raters which also included children from both diagnostic groups. It is concluded that overly positive self-judgments are not a ubiquitous finding in ADHD, but may be confined to a specific subgroup of children whose specific characteristics remain to be determined.     

Comparative Genome Analysis Provides Insights into the Evolution and Adaptation of Pseudomonas syringae pv. aesculi on Aesculus hippocastanum

A recently emerging bleeding canker disease, caused by Pseudomonas syringae pathovar aesculi (Pae), is threatening European horse chestnut in northwest Europe. Very little is known about the origin and biology of this new disease. We used the nucleotide sequences of seven commonly used marker genes to investigate the phylogeny of three strains isolated recently from bleeding stem cankers on European horse chestnut in Britain (E-Pae). On the basis of these sequences alone, the E-Pae strains were identical to the Pae type-strain (I-Pae), isolated from leaf spots on Indian horse chestnut in India in 1969. The phylogenetic analyses also showed that Pae belongs to a distinct clade of P. syringae pathovars adapted to woody hosts. We generated genome-wide Illumina sequence data from the three E-Pae strains and one strain of I-Pae. Comparative genomic analyses revealed pathovar-specific genomic regions in Pae potentially implicated in virulence on a tree host, including genes for the catabolism of plant-derived aromatic compounds and enterobactin synthesis. Several gene clusters displayed intra-pathovar variation, including those encoding type IV secretion, a novel fatty acid biosynthesis pathway and a sucrose uptake pathway. Rates of single nucleotide polymorphisms in the four Pae genomes indicate that the three E-Pae strains diverged from each other much more recently than they diverged from I-Pae. The very low genetic diversity among the three geographically distinct E-Pae strains suggests that they originate from a single, recent introduction into Britain, thus highlighting the serious environmental risks posed by the spread of an exotic plant pathogenic bacterium to a new geographic location. The genomic regions in Pae that are absent from other P. syringae pathovars that infect herbaceous hosts may represent candidate genetic adaptations to infection of the woody parts of the tree.     

Defective Secretion of Islet Hormones in Chromogranin-B Deficient Mice

Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to β-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined.     

Mechanical Analysis of Feeding Behavior in the Extinct “Terror Bird” Andalgalornis steulleti (Gruiformes: Phorusrhacidae)

The South American phorusrhacid bird radiation comprised at least 18 species of small to gigantic terrestrial predators for which there are no close modern analogs. Here we perform functional analyses of the skull of the medium-sized (∼40 kg) patagornithine phorusrhacid Andalgalornis steulleti (upper Miocene–lower Pliocene, Andalgalá Formation, Catamarca, Argentina) to assess its mechanical performance in a comparative context. Based on computed tomographic (CT) scanning and morphological analysis, the skull of Andalgalornis steulleti is interpreted as showing features reflecting loss of intracranial immobility. Discrete anatomical attributes permitting such cranial kinesis are widespread phorusrhacids outgroups, but this is the first clear evidence of loss of cranial kinesis in a gruiform bird and may be among the best documented cases among all birds. This apomorphic loss is interpreted as an adaptation for enhanced craniofacial rigidity, particularly with regard to sagittal loading. We apply a Finite Element approach to a three-dimensional (3D) model of the skull. Based on regression analysis we estimate the bite force of Andalgalornis at the bill tip to be 133 N. Relative to results obtained from Finite Element Analysis of one of its closest living relatives (seriema) and a large predatory bird (eagle), the phorusrhacid''s skull shows relatively high stress under lateral loadings, but low stress where force is applied dorsoventrally (sagittally) and in “pullback” simulations. Given the relative weakness of the skull mediolaterally, it seems unlikely that Andalgalornis engaged in potentially risky behaviors that involved subduing large, struggling prey with its beak. We suggest that it either consumed smaller prey that could be killed and consumed more safely (e.g., swallowed whole) or that it used multiple well-targeted sagittal strikes with the beak in a repetitive attack-and-retreat strategy.     

Timing the generation of distinct retinal cells by homeobox proteins

The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). Furthermore, by in vivo lipofection of “sensors” in which green fluorescent protein translation is under control of the 3′ untranslated region (UTR), we found that the 3′ UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities.     

Generation and characterization of a stable cell population releasing fluorescent HIV-1-based Virus Like Particles in an inducible way

Background  

The availability of cell lines releasing fluorescent viral particles can significantly support a variety of investigations, including the study of virus-cell interaction and the screening of antiviral compounds. Regarding HIV-1, the recovery of such biologic reagents represents a very hard challenge due to the intrinsic cytotoxicity of many HIV-1 products. We sought to overcome such a limitation by using a cell line releasing HIV-1 particles in an inducible way, and by exploiting the ability of a HIV-1 Nef mutant to be incorporated in virions at quite high levels.     

Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response

We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this approach to humans with severe hemophilia B. rAAV-2 vector expressing human F.IX was infused through the hepatic artery into seven subjects. The data show that: (i) vector infusion at doses up to 2 x 10(12) vg/kg was not associated with acute or long-lasting toxicity; (ii) therapeutic levels of F.IX were achieved at the highest dose tested; (iii) duration of expression at therapeutic levels was limited to a period of approximately 8 weeks; (iv) a gradual decline in F.IX was accompanied by a transient asymptomatic elevation of liver transaminases that resolved without treatment. Further studies suggested that destruction of transduced hepatocytes by cell-mediated immunity targeting antigens of the AAV capsid caused both the decline in F.IX and the transient transaminitis. We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression.     

2-week triple therapy for Helicobacter pylori infection is better than 1-week in clinical practice: a large prospective single-center randomized study

BACKGROUND: Proton pump inhibitor (PPI)-based triple therapies are considered the standard regimens for Helicobacter pylori eradication, but the optimal duration of these regimens is still controversial. The aim of this study was to compare the efficacy of 1-week versus 2-week triple therapies in H. pylori-positive patients. MATERIALS AND METHODS: A total of 486 consecutive H. pylori-positive patients were randomized to receive omeprazole, 20 mg b.i.d., clarithromycin 500 mg b.i.d., and either amoxicillin 1 g b.i.d. or metronidazole 500 mg b.i.d. for 1 or 2 weeks. Upper gastrointestinal endoscopy and histology were performed at entry and 2 months after the end of therapy. H. pylori status was defined according to histology and urea breath test. RESULTS: At intention-to-treat analysis, 2-week therapy with omeprazole, amoxicillin, and clarithromycin achieved a significantly higher eradication rate than 1- or 2-week regimens with metronidazole (70% versus 52%, p = .003, versus 56%, p < .01) and the same therapy for 1-week (70% versus 57%, p = .05). At per-protocol analysis, 2-week therapy with omeprazole, amoxicillin, and clarithromycin showed a significantly higher eradication rate than 1-week of amoxicillin and metronidazole (77% versus 62%; p = .03) but no difference with 1-week same regimen (66%) or 2-week metronidazole and clarithromycin regimen (72%). Compliance and tolerability were good for all regimens. CONCLUSIONS: Two-week therapies, independently of antibiotic combination, lead to a significant increase of H. pylori eradication rate compared to 1-week therapies, with same compliance and tolerability, even if, taking account of low-eradication rates, one must question whether the triple therapy should still be used.     

Complete genome of the mutualistic, N2-fixing grass endophyte Azoarcus sp. strain BH72

Azoarcus sp. strain BH72, a mutualistic endophyte of rice and other grasses, is of agrobiotechnological interest because it supplies biologically fixed nitrogen to its host and colonizes plants in remarkably high numbers without eliciting disease symptoms. The complete genome sequence is 4,376,040-bp long and contains 3,992 predicted protein-coding sequences. Genome comparison with the Azoarcus-related soil bacterium strain EbN1 revealed a surprisingly low degree of synteny. Coding sequences involved in the synthesis of surface components potentially important for plant-microbe interactions were more closely related to those of plant-associated bacteria. Strain BH72 appears to be 'disarmed' compared to plant pathogens, having only a few enzymes that degrade plant cell walls; it lacks type III and IV secretion systems, related toxins and an N-acyl homoserine lactones-based communication system. The genome contains remarkably few mobile elements, indicating a low rate of recent gene transfer that is presumably due to adaptation to a stable, low-stress microenvironment.