Evaluating the Endophenotype Model of ADHD Neuropsychological Deficit: Results for Parents and Siblings of Children With ADHD Combined and Inattentive Subtypes.

Neurogenetic models predict neuropsychological weaknesses in the relatives of children with attention-deficit/ hyperactivity disorder (ADHD). The authors examined executive and regulatory measures in 386 relatives (307 parents, 79 siblings) of children with ADHD combined type, ADHD inattentive type, and controls. Predicted deficits were seen on trailmaking (relatives of ADHD combined type only), stop-signal reaction times (relatives of girls only), and response variability (mothers only) but not on naming or output speed. Effects generally held, even with relatives' ADHD status controlled. A neuropsychologically impaired subgroup of children with ADHD had relatives with clear neuropsychological weaknesses. The authors conclude that a neurogenetic model of ADHD etiology is supportable only for a subset of executive functions and that neuropsychological heterogeneity warrants more examination in ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Demands on Attention and the Role of Response Priming in Visual Discrimination of Feature Conjunctions.

This study examined how response mapping of features within single- and multiple-feature targets affects decision-based processing and attentional capacity demands. Observers judged the presence or absence of 1 or 2 target features within an object either presented alone or with distractors. Judging the presence of 2 features relative to the less discriminable of these features alone was faster (conjunction benefits) when the task-relevant features differed in discriminability and were consistently mapped to responses. Conjunction benefits were attributed to asynchronous decision priming across attended, task-relevant dimensions. A failure to find conjunction benefits for disjunctive conjunctions was attributed to increased memory demands and variable feature-response mapping for 2- versus single-feature targets. Further, attentional demands were similar between single- and 2-feature targets when response mapping, memory demands, and discriminability of the task-relevant features were equated between targets. Implications of the findings for recent attention models are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Personalcasting: Tailored Broadcast News

Broadcast news sources and newspapers provide society with the vast majority of real-time information. Unfortunately, cost efficiencies and real-time pressures demand that producers, editors, and writers select and organize content for stereotypical audiences. In this article we illustrate how content understanding, user modeling, and tailored presentation generation promise personalcasts on demand. Specifically, we report on the design and implementation of a personalized version of a broadcast news understanding system, MITRE’s Broadcast News Navigator (BNN), that tracks and infers user content interests and media preferences. We report on the incorporation of Local Context Analysis to both expand the user’s original query to the most related terms in the corpus, as well as to allow the user to provide interactive feedback to enhance the relevance of selected newsstories. We describe an empirical study of the search for stories on ten topics from a video corpus. By personalizing both the selection of stories and the form in which they are delivered, we provide users with tailored broadcast news. This individual news personalization provides more fine-grained content tailoring than current personalized television program level recommenders and does not rely on externally provided program metadata.     

Sleep Modulates Alcohol Toxicity in Drosophila

Alcohol abuse is a significant public health problem. While considerable research has shown that alcohol use affects sleep, little is known about the role of sleep deprivation in alcohol toxicity. We investigated sleep as a factor modulating alcohol toxicity using Drosophila melanogaster, a model for studies of sleep, alcohol, and aging. Following 24 h of sleep deprivation using a paradigm that similarly affects males and females and induces rebound sleep, flies were given binge-like alcohol exposures. Sleep deprivation increased mortality, with no sex-dependent differences. Sleep deprivation also abolished functional tolerance measured at 24 h after the initial alcohol exposure, although there was no effect on alcohol absorbance or clearance. We investigated the effect of chronic sleep deprivation using mutants with decreased sleep, insomniac and insulin-like peptide 2, finding increased alcohol mortality. Furthermore, we investigated whether pharmacologically inducing sleep prior to alcohol exposure using the GABA_A-receptor agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) mitigated the effects of alcohol toxicity on middle-aged flies, flies with environmentally disrupted circadian clocks, and flies with short sleep. Pharmacologically increasing sleep prior to alcohol exposure decreased alcohol-induced mortality. Thus, sleep prior to binge-like alcohol exposure affects alcohol-induced mortality, even in vulnerable groups such as aging flies and those with circadian dysfunction.     

Optical and Flame-Retardant Properties of a Series of Polyimides Containing Side Chained Bulky Phosphaphenanthrene Units

Among the multitude of polymers with carbon-based macromolecular architectures that easily ignite in certain applications where short circuits may occur, polyimide has evolved as a class of polymers with high thermal stability while exhibiting intrinsic flame retardancy at elevated temperatures via a char-forming mechanism. However, high amounts of aromatic rings in the macromolecular backbone are required for these results, which may affect other properties such as film-forming capacity or mechanical properties; thus, much work has been done to structurally derivatize or make hybrid polyimide systems. In this respect, flexible polyimide films (PI(1–4)) containing bulky 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) units have been developed starting from commercial dianhydrides and an aromatic diamine containing two side chain bulky DOPO groups. The chemical structure of PI(1–4)) was characterized by ¹H NMR, ¹³C NMR and ³¹P NMR spectroscopy. The optical properties, including absorption and luminescence spectra of these polymers, were analyzed. All polyimides containing DOPO derivatives emitted blue light with an emission maxima in the range of 340–445 nm, in solvents such as N,N-dimethylformamide, N-methyl-2-pyrrolidone, chloroform, and N,N-dimethylacetamide, while green light emission (λ_em = 487 nm for PI-4) was evidenced in a thin-film state. The thermal decomposition mechanism and flame-retardant behavior of the resulting materials were investigated by pyrolysis-gas-chromatography spectrometry (Py-GC), scanning electron microscopy (SEM), EDX maps and FTIR spectroscopy. The residues resulting from the TGA experiments were examined by SEM microscopy images and FTIR spectra to understand the pyrolysis mechanism.     

Differential Responses to Sigma-1 or Sigma-2 Receptor Ablation in Adiposity,Fat Oxidation,and Sexual Dimorphism

Obesity is increasing at epidemic rates across the US and worldwide, as are its co-morbidities, including type-2 diabetes and cardiovascular disease. Thus, targeted interventions to reduce the prevalence of obesity are of the utmost importance. The sigma-1 receptor (S1R) and sigma-2 receptor (S2R; encoded by Tmem97) belong to the same class of drug-binding sites, yet they are genetically distinct. There are multiple ongoing clinical trials focused on sigma receptors, targeting diseases ranging from Alzheimer’s disease through chronic pain to COVID-19. However, little is known regarding their gene-specific role in obesity. In this study, we measured body composition, used a comprehensive laboratory-animal monitoring system, and determined the glucose and insulin tolerance in mice fed a high-fat diet. Compared to Sigmar1+/+ mice of the same sex, the male and female Sigmar1−/− mice had lower fat mass (17% and 12% lower, respectively), and elevated lean mass (16% and 10% higher, respectively), but S1R ablation had no effect on their metabolism. The male Tmem97−/− mice exhibited 7% lower fat mass, 8% higher lean mass, increased volumes of O₂ and CO₂, a decreased respiratory exchange ratio indicating elevated fatty-acid oxidation, and improved insulin tolerance, compared to the male Tmem97+/+ mice. There were no changes in any of these parameters in the female Tmem97−/− mice. Together, these data indicate that the S1R ablation in male and female mice or the S2R ablation in male mice protects against diet-induced adiposity, and that S2R ablation, but not S1R deletion, improves insulin tolerance and enhances fatty-acid oxidation in male mice. Further mechanistic investigations may lead to translational strategies to target differential S1R/S2R regulations and sexual dimorphism for precision treatments of obesity.     

Improved Bladder Tumor RNA Isolation from Archived Tissues Using Methylene Blue for Normalization,Multiplex RNA Hybridization,Sequencing and Subtyping

Methylene blue (MB) is a dye used for histology with clinical importance and intercalates into nucleic acids. After MB staining of formalin fixed paraffin embedded (FFPE) muscle invasive bladder cancer (MIBC) and normal urothelium, specific regions could be microdissected. It is not known if MB influences RNA used for gene expression studies. Therefore, we analyzed MIBC using five different RNA isolation methods comparing patient matched FFPE and fresh frozen (FF) tissues pre-stained with or without MB. We demonstrate a positive impact of MB on RNA integrity with FF tissues using real time PCR with no interference of its chemical properties. FFPE tissues showed no improvement of RNA integrity, which we propose is due to formalin induced nucleotide crosslinks. Using direct multiplex RNA hybridization the best genes for normalization of MIBC and control tissues were identified from 34 reference genes. In addition, 5SrRNA and 5.8SrRNA were distinctive reference genes detecting <200 bp fragments important for mRNA analyses. Using these normalized RNAs from MB stained MIBC and applying multiplex RNA hybridization and mRNA sequencing, a minimal gene expression panel precisely identified luminal and basal MIBC tumor subtypes, important for diagnosis, prognosis and chemotherapy response.     

Segmentation of Colour Images with Highlights and Shadows sing Fuzzy-like Reasoning

In this paper, a fuzzy-like technique is presented that resolves several difficult issues related to image segmentation, such as highlights and shadows. Large, relatively continuous, areas within an image are usually easy to segment, and the pixels included within different segments are often determined by using derived edge information. However, in many cases, pixels which lie between segments or in high frequency areas of an image cannot be easily categorised as belonging to any particular segments. Typically, according to the dichromatic reflection model, these pixels may belong to the matte, highlight or shadow area of the closest segment; or, in association with neighbouring pixels, they make up a separate smaller segment. The dichromatic reflection model is applied here to merge highlight and shadow areas with matte areas in an image. By segmenting those pixels into proper regions, the proposed fuzzy-like reasoning approach provides a more human-like segmentation of images.     

Effects of Physiological and Pathological Urea Concentrations on Human Microvascular Endothelial Cells

Urea is the uremic toxin accumulating with the highest concentration in the plasma of chronic kidney disease (CKD) patients, not being completely cleared by dialysis. Urea accumulation is reported to exert direct and indirect side effects on the gastrointestinal tract, kidneys, adipocytes, and cardiovascular system (CVS), although its pathogenicity is still questioned since studies evaluating its side effects lack homogeneity. Here, we investigated the effects of physiological and pathological urea concentrations on a human endothelial cell line from the microcirculation (Human Microvascular Endothelial Cells-1, HMEC-1). Urea (5 g/L) caused a reduction in the proliferation rate after 72 h of exposure and appeared to be a potential endothelial-to-mesenchymal transition (EndMT) stimulus. Moreover, urea induced actin filament rearrangement, a significant increase in matrix metalloproteinases 2 (MMP-2) expression in the medium, and a significant up- or down-regulation of other EndMT biomarkers (keratin, fibrillin-2, and collagen IV), as highlighted by differential proteomic analysis. Among proteins whose expression was found to be significantly dysregulated following exposure of HMEC-1 to urea, dimethylarginine dimethylaminohydrolase (DDAH) and vasorin turned out to be down-regulated. Both proteins have been directly linked to cardiovascular diseases (CVD) by in vitro and in vivo studies. Future experiments will be needed to deepen their role and investigate the signaling pathways in which they are involved to clarify the possible link between CKD and CVD.