Laminar Thickness Alterations in the Fronto-Parietal Cortical Mantle of Patients with Attention-Deficit/Hyperactivity Disorder

Although Attention-Deficit/Hyperactivity Disorder (ADHD) was initially regarded as a disorder exclusive to childhood, nowadays its prevalence in adulthood is well established. The development of novel techniques for quantifying the thickness of the cerebral mantle allows the further exploration of the neuroanatomical profiles underlying the child and adult form of the disorder. To examine the cortical mantle in children and adults with ADHD, we applied a vertex-wise analysis of cortical thickness to anatomical brain MRI scans acquired from children with (n = 43) and without ADHD (n = 41), as well as a group of adult neurotypical individuals (n = 31), adult patients with a history of stimulant treatment (n = 31) and medication-naïve adults with ADHD (n = 24). We observed several clusters of reduced laminar cortical thickness in ADHD patients in comparison to neurotypical individuals. These differences were primarily located in the dorsal attention network, including the bilateral inferior and superior parietal cortex and a section of the frontal cortex (centered on the superior frontal and precentral gyrus bilaterally). Further laminar thickness deficits were observed in the bilateral orbitofrontal cortex and medial occipital cortex. The deficits in the cortical surface were especially pronounced in the child sample, while adult patients showed a more typical laminar thickness across the cerebral mantle. These findings show that the neuroanatomical profile of ADHD, especially the childhood form of the disorder, involves robust alterations in the cortical mantle, which are most prominent in brain regions subserving attentional processing.     

In-depth characterization of viral isolates from plasma and cells compared with plasma circulating quasispecies in early HIV-1 infection

Background

The use of in vitro models to unravel the phenotypic characteristics of circulating viral variants is key to understanding HIV-1 pathogenesis but limited by the availability of primary viral isolates from biological samples. However, overall in vivo genetic variability of HIV-1 within a subject may not be reflected in the viable viral population obtained after isolation. Although several studies have tried to determine whether viral populations expanded in vitro are representative of in vivo findings, the answer remains unclear due to the reduced number of clonal sequences analyzed or samples compared. In order to overcome previous experimental limitations, here we applied Deep Pyrosequencing (DPS) technology in combination with phenotypic experiments to analyze and compare with unprecedented detail the composition of viral isolates and in vivo quasispecies.

Methodology/Principal Findings

We amplified by DPS HIV-1 genomic regions covering gag, protease, integrase and env-V3 to characterize paired isolates from plasma and peripheral blood mononuclear cells and compare them with total plasma viral RNA in four recently HIV-1 infected subjects. Our study demonstrated the presence of unique haplotypes scattered between sample types with conservation of major variants. In addition, no differences in intra- and inter-population encoded protein variability were found between the different types of isolates or when these were compared to plasma viral RNA within subjects. Additionally, in vitro experiments demonstrated phenotypic similarities in terms of replicative capacity and co-receptor usage between viral isolates and plasma viral RNA.

Conclusion

This study is the first in-depth comparison and characterization of viral isolates from different sources and plasma circulating quasispecies using DPS in recently HIV-1 infected subjects. Our data supports the use of primary isolates regardless of their plasma or cellular origin to define genetic variability and biological traits of circulating HIV-1 quasispecies.     

Inhibition of specific NF-κB activity contributes to the tumor suppressor function of 14-3-3σ in breast cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting.     

The Péclet effect on leaf water enrichment correlates with leaf hydraulic conductance and mesophyll conductance for CO(2)

Leaf water gets isotopically enriched through transpiration, and diffusion of enriched water through the leaf depends on transpiration flow and the effective path length (L). The aim of this work was to relate L with physiological variables likely to respond to similar processes. We studied the response to drought and vein severing of leaf lamina hydraulic conductance (K_lamina), mesophyll conductance for CO₂ (g_m) and leaf water isotope enrichment in Vitis vinifera L cv. Grenache. We hypothesized that restrictions in water pathways would reduce K_lamina and increase L. As a secondary hypothesis, we proposed that, given the common pathways for water and CO₂ involved, a similar response should be found in g_m. Our results showed that L was strongly related to mesophyll variables, such as K_lamina or g_m across experimental drought and vein‐cutting treatments, showing stronger relationships than with variables included as input parameters for the models, such as transpiration. Our findings were further supported by a literature survey showing a close link between L and leaf hydraulic conductance (K_leaf = 31.5 × L^?0.43, r² = 0.60, n = 24). The strong correlation found between L, K_lamina and g_m supports the idea that water and CO₂ share an important part of their diffusion pathways through the mesophyll.     

<Emphasis Type="Italic">Fastbreak</Emphasis>: a tool for analysis and visualization of structural variations in genomic data

Genomic studies are now being undertaken on thousands of samples requiring new computational tools that can rapidly analyze data to identify clinically important features. Inferring structural variations in cancer genomes from mate-paired reads is a combinatorially difficult problem. We introduce Fastbreak, a fast and scalable toolkit that enables the analysis and visualization of large amounts of data from projects such as The Cancer Genome Atlas.     

The rapid light response of leaf hydraulic conductance: new evidence from two experimental methods

Previous studies have shown a rapid enhancement in leaf hydraulic conductance (K(leaf)) from low to high irradiance (from <10 to >1000 micromol photons m(-2) s(-1)), using the high-pressure flow meter (HPFM), for 7 of 14 tested woody species. However, theoretical suggestions have been made that this response might arise as an artifact of the HPFM. We tested the K(leaf) light response for six evergreen species using refined versions of the rehydration kinetics method (RKM) and the evaporative flux method (EFM). We found new evidence for a rapid, 60% to 100% increase in K(leaf) from low to high irradiance for three species. In the RKM, the leaf rehydration time constant declined by up to 70% under high irradiance relative to darkness. In the EFM, under higher irradiance, the flow rate increased disproportionately to the water potential gradient. Combining our data with those of previous studies, we found that heterobaric species, i.e. those with bundle sheath extensions (BSEs) showed a twofold greater K(leaf) light response on average than homobaric species, i.e. those without BSEs. We suggest further research to characterize this substantial dynamic at the nexus of plant light- and water-relations.     

Inheritance and linkage relationships of ten isozyme genes in hazelnut

Summary The inheritance of 6-phosphogluconate dehydrogenase (6PGD), malate dehydrogenase (MHD), aconitase (ACO), phosphoglucomutase (PGM), phosphoglucoisomerase (PGI), and glutamate-oxalacetate transaminase (GOT) polymorphic isozymes was studied in leaf extracts of nine hazelnut progenies using horizontal starch gel electrophoresis. Evidence of Mendelian inheritance was obtained for ten loci: 6-Pgd-2, Mdh-1, Aco-1, Aco-2, Pgm-1, Pgm-2, Pgm-3, Pgi-2, Pgi-3, and Got-2, which permitted the analysis of 28 alleles (2.8 per locus). The presence of null alleles was detected in Pgm-1 and Pgm-3. Joint segregation analysis of pairs of isozymes revealed four linkages: Mdh-1-Pgi-2, Aco-2-Pgm-2, Pgm-1-Pgm-3, and 6Pdg-2-Pgm-2.     

Light-dependent spin trapping of hydroxyl radical from human erythrocytes.

The generation of reactive oxygen species from human erythrocytes has previously been demonstrated. Furthermore, erythrocytic protoporphyrin IX has been shown to generate superoxide and singlet oxygen when exposed to light. These findings suggest that a component of erythrocytic reactive oxygen species production may be light-dependent. By inhibiting erythrocyte superoxide dismutase, catalase, and glutathione peroxidase with N,N-diethyldithiocarbamate or sodium cyanide, we demonstrate the light-dependent generation of hydroxyl radical in human erythrocytes using spin trapping/Electron Spin Resonance spectroscopy. This finding may be significant in tissues where blood is exposed to light, such as in the eye.     

Calcium chelator Quin 2 prevents hydrogen-peroxide-induced DNA breakage and cytotoxicity

Exposure of cultured Chinese hamster ovary (CHO) cells to hydrogen peroxide results in the production of extensive DNA breakage which can be prevented by the intracellular calcium chelator Quin 2. This effect occurs at Quin 2 AM concentrations as low as 0.1 microM and is maximal at 1 microM. Addition of the extracellular calcium chelator, EGTA, does not affect the level of DNA breakage generated by H2O2. Quin 2 also significantly reduces cellular toxicity caused by the oxidant. Experiments with spin-trapping techniques demonstrate that Quin 2 does not affect the formation of hydroxyl radicals generated by the action of Fe2+ on H2O2. Quin 2 at high concentrations, similar to those reached within the cell, actually enhanced generation of hydroxyl radical in the absence of other iron chelators under our experimental conditions. These results suggest that H2O2 or H2O2-derived radicals do not directly induce DNA strand breakage in intact mammalian cells; rather, these radicals may disturb intracellular Ca2+ homeostasis which results in secondary reactions ultimately leading to DNA strand breakage. In addition to strand breakage, membrane and protein oxidation probably contribute to the cytotoxic effect of H2O2.     

Antitumor action of bovine seminal ribonuclease

Unlike the bovine pancreatic ribonuclease (RNAase A), bovine seminal ribonuclease (BS RNAase) displays various biological activities including antitumor cytotoxicity. To learn more about its antitumor activity, we investigated BS RNAase effect on athymic nude mice bearing various tumors. BS RNAase (250 μg per mouse per day) was administered to the mice with prostate carcinoma for three weeks by three different routes (intraperitoneally—i.p., subcutaneously—s.c., and intratumorally—i.t.). Administration i.p. was ineffective, while s.c. administration reduced significantly size of tumors and i.t. administration abolished half of the tumors in treated mice. The i.t. administration of BS RNase to nude mice bearing melanoma showed even better results. Eighty % of mice were without tumors and in the other mice the tumors were significantly diminished. The best antitumor effect was obtained in case of seminoma. All mice bearing this tumor were cured after ten doses of BS RNAase.