A Wider and Deeper Peptide-Binding Groove for the Class I Molecules from B15 Compared with B19 Chickens Correlates with Relative Resistance to Marek's Disease.

The chicken MHC is known to confer decisive resistance or susceptibility to various economically important pathogens, including the iconic oncogenic herpesvirus that causes Marek's disease (MD). Only one classical class I gene, BF2, is expressed at a high level in chickens, so it was relatively easy to discern a hierarchy from well-expressed thermostable fastidious specialist alleles to promiscuous generalist alleles that are less stable and expressed less on the cell surface. The class I molecule BF2*1901 is better expressed and more thermostable than the closely related BF2*1501, but the peptide motif was not simpler as expected. In this study, we confirm for newly developed chicken lines that the chicken MHC haplotype B15 confers resistance to MD compared with B19. Using gas phase sequencing and immunopeptidomics, we find that BF2*1901 binds a greater variety of amino acids in some anchor positions than does BF2*1501. However, by x-ray crystallography, we find that the peptide-binding groove of BF2*1901 is narrower and shallower. Although the self-peptides that bound to BF2*1901 may appear more various than those of BF2*1501, the structures show that the wider and deeper peptide-binding groove of BF2*1501 allows stronger binding and thus more peptides overall, correlating with the expected hierarchies for expression level, thermostability, and MD resistance. Our study provides a reasonable explanation for greater promiscuity for BF2*1501 compared with BF2*1901, corresponding to the difference in resistance to MD.

Household Transmission of SARS-CoV-2 from Humans to Pets, Washington and Idaho, USA.

SARS-CoV-2 likely emerged from an animal reservoir. However, the frequency of and risk factors for interspecies transmission remain unclear. We conducted a community-based study in Idaho, USA, of pets in households that had >1 confirmed SARS-CoV-2 infections in humans. Among 119 dogs and 57 cats, clinical signs consistent with SARS-CoV-2 were reported for 20 dogs (21%) and 19 cats (39%). Of 81 dogs and 32 cats sampled, 40% of dogs and 43% of cats were seropositive, and 5% of dogs and 8% of cats were PCR positive. This discordance might be caused by delays in sampling. Respondents commonly reported close human‒animal contact and willingness to take measures to prevent transmission to their pets. Reported preventive measures showed a slightly protective but nonsignificant trend for both illness and seropositivity in pets. Sharing of beds and bowls had slight harmful effects, reaching statistical significance for sharing bowls and seropositivity.

Pushing the Limits on the Intestinal Crossing of Metal-Organic Frameworks: An Ex Vivo and In Vivo Detailed Study.

Biocompatible nanoscaled metal-organic frameworks (nanoMOFs) have been widely studied as drug delivery systems (DDSs), through different administration routes, with rare examples in the convenient and commonly used oral administration. So far, the main objective of nanoMOFs as oral DDSs was to increase the bioavailability of the cargo, without considering the MOF intestinal crossing with potential advantages (e.g., increasing drug availability, direct transport to systemic circulation). Thus, we propose to address the direct quantification and visualization of MOFs' intestinal bypass. For that purpose, we select the microporous Fe-based nanoMOF, MIL-127, exhibiting interesting properties as a nanocarrier (great biocompatibility, large porosity accessible to different drugs, green and multigram scale synthesis, outstanding stability along the gastrointestinal tract). Additionally, the outer surface of MIL-127 was engineered with the biopolymer chitosan (CS@MIL-127) to improve the nanoMOF intestinal permeation. The biocompatibility and intestinal crossing of nanoMOFs is confirmed using a simple and relevant in vivo model, Caenorhabditis elegans; these worms are able to ingest enormous amounts of nanoMOFs (up to 35 g per kg of body weight). Finally, an ex vivo intestinal model (rat) is used to further support the nanoMOFs' bypass across the intestinal barrier, demonstrating a fast crossing (only 2 h). To the best of our knowledge, this report on the intestinal crossing of intact nanoMOFs sheds light on the safe and efficient application of MOFs as oral DDSs.

Towards improving the capacity of UiO-66 for antibiotic elimination from contaminated water.

Antibiotics are found in natural waters, raising concern about their human and environmental toxicity and the wide occurrence of antibiotic resistant bacteria. The antibiotic resistance crisis is attributed to the overuse and misuse of these medications. Particularly, sulfamethazine (SMT), an antibiotic commonly used in pigs and cattle for the treatment of bacterial diseases, has been detected in the natural environment (soil and water). Among all the technologies developed to combat the deteriorating water quality and control antimicrobial resistance, heterogeneous photocatalysis should be highlighted for the degradation of refractory organic compounds. Here, we described the SMT adsorption and photodegradation capacity of a highly porous and robust zirconium-based MOF UiO-66 under realistic conditions, and its potential recyclability. Further, its SMT removal capacity was improved by functionalizing the MOF porosity (28.5% of SMT adsorption in 24 h for nanoUiO-66-NH2), and nanosizing the MOF (100% SMT photodegradation in only 4 h for nanoUiO-66). Finally, the safety of the formed by-product during SMT photodegradation was confirmed, reinforcing the potential of the application of UiO-66 in water remediation.

Phase-Selective Microwave Assisted Synthesis of Iron(III) Aminoterephthalate MOFs.

Iron(III) aminoterephthalate Metal-Organic Frameworks (Fe-BDC-NH2 MOFs) have been demonstrated to show potential for relevant industrial and societal applications (i.e., catalysis, drug delivery, gas sorption). Nevertheless, further analysis is required in order to achieve their commercial production. In this work, a systematic synthetic strategy has been followed, carrying out microwave (MW) assisted hydro/solvothermal reactions to rapidly evaluate the influence of different reaction parameters (e.g., time, temperature, concentration, reaction media) on the formation of the benchmarked MIL-101-NH2, MIL-88B-NH2, MIL-53-NH2 and MIL-68-NH2 solids. Characterization of the obtained solids by powder X-ray diffraction, dynamic light scattering and transmission electron microscopy allowed us to identify trends to the contribution of the evaluated parameters, such as the relevance of the concentration of precursors and the impact of the reaction medium on phase crystallization. Furthermore, we presented here for the first time the MW assisted synthesis of MIL-53-NH2 in water. In addition, pure MIL-101-NH2 was also produced in water while MIL-88-NH2 was the predominant phase obtained in ethanol. Pure phases were produced with high space-time yields, unveiling the potential of MW synthesis for MOF industrialization.

Biomarcadores para la evaluación y diagnóstico del síndrome de ojo seco: una revisión / Biomarkers for the evaluation and diagnosis of the dry eye syndrome: a review

Resumen Introducción: El síndrome de ojo seco es una enfermedad en la que se generan signos y síntomas que conducen a alteraciones oculares prolongadas, por lo tanto, es relevante establecer con precisión la etiología de la enfermedad con la finalidad de establecer el tratamiento más efectivo, de allí, la importancia del desarrollo de exámenes innovadores como son los biomarcadores, los cuales permiten identificar con mayor precisión el cuadro clínico. Por esta razón, el presente trabajo pretende describir los principales avances de los biomarcadores de la superficie ocular y reconocer su aplicación clínica para el diagnóstico de ojo seco entre los años 2013 a 2018. Metodología: Se analizó literatura sobre biomarcadores empleados para el diagnóstico del ojo seco, mediante una revisión sistemática tipo narrativa de 2013 a 2018 por medio de los descriptores controlados "Dry Eye Syndrome" "biomarkers" "tear proteins" "eye proteins" seleccionados en DeCS y Pubmed; la búsqueda arrojó 48 estudios, de los cuales seleccionamos 21 para el análisis. Resultados: Son diversas las proteínas lagrimales que pueden ser relacionadas con la presencia y ausencia de la enfermedad, es vital que los biomarcadores sean valorados como una herramienta alternativa para diagnosticar con facilidad y precisión la enfermedad del ojo seco. Discusión: Los biomarcadores permiten reconocer los procesos patógenos y biológicos del síndrome de ojo seco, al reflejar el estado de la superficie ocular en presencia o ausencia de signos y síntomas, facilitando el diagnóstico precoz, seguimiento, tratamiento y control de la enfermedad.

Abstract Introduction: Dry eye syndrome is a disease in which signs and symptoms that lead to prolonged ocular alterations occur, therefore, it is relevant to accurately establish the etiology of the disease with the configuration of establishing the most effective treatment, hence the development of innovative exams such as biomarkers selected with greater precision the clinical picture. For this reason, the present work aims to describe the main advances of biomarkers of the ocular surface and to recognize their clinical application for the diagnosis of dry eye between 2013 and 2018. Metodology: Literature on biomarkers used for the diagnosis of dry eye was analyzed, by means of a systematic narrative review from 2013 to 2018 by means of the controlled descriptors "Dry Eye Syndrome" "biomarkers" "tear proteins" "eye proteins" selected in DeCS and Pubmed; The search yielded 48 studies and 21 studies were selected for the analysis. Results: There are several tear proteins that can be related to the presence and absence of the disease, it is vital that biomarkers are evaluated as an alternative tool to easily and accurately diagnose dry eye disease. Discussion: Biomarkers allow to recognize the pathogenic and biological processes of dry eye syndrome, reflecting the state of the ocular surface in the presence or absence of signs and symptoms, facilitating early diagnosis, monitoring, treatment and control of the disease.

Cognitive Correlates of Hippocampal Atrophy and Ventricular Enlargement in Adults with or without Mild Cognitive Impairment.

We analyzed structural magnetic resonance imaging data from 58 cognitively normal and 101 mild cognitive impairment subjects. We used a general linear regression model to study the association between cognitive performance with hippocampal atrophy and ventricular enlargement using the radial distance method. Bilateral hippocampal atrophy was associated with baseline and longitudinal memory performance. Left hippocampal atrophy predicted longitudinal decline in visuospatial function. The multidomain ventricular analysis did not reveal any significant predictors.

Piezoelectric Ceramics of the (1 - x)Bi0.50Na0.50TiO3-xBa0.90Ca0.10TiO3 Lead-Free Solid Solution: Chemical Shift of the Morphotropic Phase Boundary, a Case Study for x = 0.06.

Research and development of lead-free piezoelectric materials are still the hottest topics in the field of piezoelectricity. One of the most promising lead-free family of compounds to replace lead zirconate-titanate for actuators is that of Bi0.50Na0.50TiO3 (BNT) based solid solutions. The pseudo-binary (1 - x)Bi0.50Na0.50TiO3-xBa1 - yCayTiO3 system has been proposed for high temperature capacitors and not yet fully explored as piezoelectric material. In this work, the solid solution with x = 0.06 and y = 0.10 was obtained by two different synthesis routes: solid state and Pechini, aiming at using reduced temperatures, both in synthesis (<800 °C) and sintering (<1150 °C), while maintaining appropriated piezoelectric performance. Crystal structure, ceramic grain size, and morphology depend on the synthesis route and were analyzed by X-ray diffraction, together with scanning and transmission electron microscopy. The effects of processing and ceramic microstructure on the structural, dielectric, ferroelectric, and piezoelectric properties were discussed in terms of a shift of the Morphotropic Phase Boundary, chemically induced by the synthesis route.

Ablation dynamics of Co/ZnS targets under double pulse femtosecond laser irradiation.

Femtosecond lasers, used as tools to investigate the ablation dynamics of solids, can help to develop strategies to control the deposition of nanomaterials by pulsed laser ablation. In this work, Co/ZnS targets, potential candidates for the synthesis of diluted magnetic semiconductor materials, are irradiated by sequences of two femtosecond laser pulses delayed in the picosecond time scale. The ionic composition of the ablation plasma and the dependence of the ion signals on the interpulse delay and relative fluence are determined by time-of-flight mass spectrometry. The results show that, when pulses of different fluence are used, highly asymmetric ion yields are obtained, with more intense ion signals detected when the lower fluence pulse is temporally ahead. The comparison between asymmetric and equal fluence double pulse ablation dynamics provides some understanding of the different processes that modify the properties of the layer irradiated by the first pulse and of the mechanisms affecting the coupling of the delayed pulse into the material. The final outcome of the double pulse irradiation is characterized through the analysis of the deposits produced upon ablation.

Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures.

BACKGROUND: The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort. METHODS: We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF ß-amyloid 1-42 (Aß42) ≤ 192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥ 1.5. We trained our classifier in the subcohort with CSF Aß42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aß42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia. RESULTS: The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%. CONCLUSIONS: Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%).

Polyrotaxane-mediated self-assembly of gold nanospheres into fully reversible supercrystals.

The use of a thiol-functionalized nonionic surfactant to stabilize spherical gold nanoparticles in water induces the spontaneous formation of polyrotaxanes at the nanoparticle surface in the presence of the macrocycle α-cyclodextrin. Whereas using an excess of surfactant an amorphous gold nanocomposite is obtained, under controlled drying conditions the self-assembly between the surface supramolecules provides large and homogenous supercrystals with hexagonal close packing of nanoparticles. Once formed, the self-assembled supercrystals can be fully redispersed in water. The reversibility of the crystallization process may offer an excellent reusable material to prepare gold nanoparticle inks and optical sensors with the potential to be recovered after use.

ApoE4 effects on automated diagnostic classifiers for mild cognitive impairment and Alzheimer's disease.

Biomarkers are the only feasible way to detect and monitor presymptomatic Alzheimer's disease (AD). No single biomarker can predict future cognitive decline with an acceptable level of accuracy. In addition to designing powerful multimodal diagnostic platforms, a careful investigation of the major sources of disease heterogeneity and their influence on biomarker changes is needed. Here we investigated the accuracy of a novel multimodal biomarker classifier for differentiating cognitively normal (NC), mild cognitive impairment (MCI) and AD subjects with and without stratification by ApoE4 genotype. 111 NC, 182 MCI and 95 AD ADNI participants provided both structural MRI and CSF data at baseline. We used an automated machine-learning classifier to test the ability of hippocampal volume and CSF Aß, t-tau and p-tau levels, both separately and in combination, to differentiate NC, MCI and AD subjects, and predict conversion. We hypothesized that the combined hippocampal/CSF biomarker classifier model would achieve the highest accuracy in differentiating between the three diagnostic groups and that ApoE4 genotype will affect both diagnostic accuracy and biomarker selection. The combined hippocampal/CSF classifier performed better than hippocampus-only classifier in differentiating NC from MCI and NC from AD. It also outperformed the CSF-only classifier in differentiating NC vs. AD. Our amyloid marker played a role in discriminating NC from MCI or AD but not for MCI vs. AD. Neurodegenerative markers contributed to accurate discrimination of AD from NC and MCI but not NC from MCI. Classifiers predicting MCI conversion performed well only after ApoE4 stratification. Hippocampal volume and sex achieved AUC = 0.68 for predicting conversion in the ApoE4-positive MCI, while CSF p-tau, education and sex achieved AUC = 0.89 for predicting conversion in ApoE4-negative MCI. These observations support the proposed biomarker trajectory in AD, which postulates that amyloid markers become abnormal early in the disease course while markers of neurodegeneration become abnormal later in the disease course and suggests that ApoE4 could be at least partially responsible for some of the observed disease heterogeneity.

Development of a 5-plex SILAC method tuned for the quantitation of tyrosine phosphorylation dynamics.

The propagation of phosphorylation downstream of receptor tyrosine kinases is a key dynamic cellular event involved in signal transduction, which is often deregulated in disease states such as cancer. Probing phosphorylation dynamics is therefore crucial for understanding receptor tyrosine kinases' function and finding ways to inhibit their effects. MS methods combined with metabolic labeling such as stable isotope labeling with amino acids in cell culture (SILAC) have already proven successful in deciphering temporal phosphotyrosine perturbations. However, they are limited in terms of multiplexing, and they also are time consuming, because several experiments need to be performed separately. Here, we introduce an innovative approach based on 5-plex SILAC that allows monitoring of phosphotyrosine signaling perturbations induced by a drug treatment in one single experiment. Using this new labeling strategy specifically tailored for phosphotyrosines, it was possible to generate the time profiles for 318 unique phosphopeptides belonging to 215 proteins from an erlotinib-treated breast cancer cell line model. Hierarchical clustering of the time profiles followed by pathway enrichment analysis highlighted epidermal growth factor receptor (EGFR or ErbB1) and ErbB2 signaling as the major pathways affected by erlotinib, thereby validating the method. Moreover, based on the similarity of its time profile to those of other proteins in the ErbB pathways, the phosphorylation at Tyr453 of protein FAM59A, a recently described adaptor of EGFR, was confirmed as tightly involved in the signaling cascade. The present investigation also demonstrates the remote effect of EGFR inhibition on ErbB3 phosphorylation sites such as Tyr1289 and Tyr1328, as well as a potential feedback effect on Tyr877 of ErbB2. Overall, the 5-plex SILAC is a straightforward approach that extends sample multiplexing and builds up the arsenal of methods for tyrosine phosphorylation dynamics.

Quantitative chemical proteomics profiling differentiates erlotinib from gefitinib in EGFR wild-type non-small cell lung carcinoma cell lines.

Although both erlotinib and gefitinib target the EGF receptor (EGFR), erlotinib is effective in patients with EGFR wild-type or mutated tumors, whereas gefitinib is only beneficial for patients with activating mutations. To determine whether these differences in clinical outcomes can be attributed to their respective protein interaction profiles, a label-free, quantitative chemical proteomics study was conducted. Using this method, 24 proteins were highlighted in the binding profiles of erlotinib and gefitinib. Unlike gefinitib, erlotinib displaced the ternary complex formed by integrin-linked kinase (ILK), α-parvin, and PINCH (IPP). The docking of erlotinib in the three-dimensional structure of ILK showed that erlotinib has the ability to bind to the ATP-binding site, whereas gefitinib is unlikely to bind with high affinity. As the IPP complex has been shown to be involved in epithelial-to-mesenchymal transition (EMT) and erlotinib sensitivity has been correlated with EMT status, we used a cellular model of inducible transition and observed that erlotinib prevented EMT in a more efficient way than gefitinib by acting on E-cadherin expression as well as on IPP levels. A retrospective analysis of the MERIT trial indicated that, besides a high level of E-cadherin, a low level of ILK could be linked to clinical benefit with erlotinib. In conclusion, we propose that, in an EGFR wild-type context, erlotinib may have a complementary mode of action by inhibiting IPP complex activities, resulting in the slowing down of the metastatic process of epithelial tumors.

Microwave-assisted synthesis, microstructure, and physical properties of rare-earth chromites.

The full rare-earth (RE) chromites series (RE)CrO(3) with an orthorhombic distorted (Pnma) perovskite structure and the isostructural compound YCrO(3) can be synthesized through a simple microwave-assisted technique, yielding high-quality materials. Magnetization measurements evidence that the Néel temperature for antiferromagnetic Cr(3+)-Cr(3+) ordering strongly depends on the RE(3+) ionic radius (IOR), and a rich variety of different magnetic spin interactions exists. Dielectric spectroscopy on sintered pellets indicates electronic inhomogeneity in all samples as manifested by the presence of at least two dielectric relaxation processes associated with grain boundary and grain interior bulk contributions. X-ray diffraction, Raman spectroscopy, and temperature-dependent dielectric permittivity data do not indicate potential noncentrosymmetry in the crystal or concomitant ferroelectricity. Strong correlations between the magnetic and dielectric properties were not encountered, and microwave-synthesized (RE)CrO(3) may not be classified as magnetoelectric or multiferroic materials.

Effects of a gonadotropin-releasing hormone vaccine on ovarian cyclicity and uterine morphology of an Asian elephant (Elephas maximus).

This report describes the successful use of a gonadotropin-releasing hormone (GnRH) vaccine to suppress ovarian steroidogenic activity and to treat hemorrhage and anemia associated with reproductive tract pathology in a 59-year-old Asian elephant (Elephas maximus). The Repro-BLOC GnRH vaccine was administered subcutaneously as a series of 4 boosters of increasing dose from 3 to 30 mg of recombinant ovalbumin-GnRH fusion protein given at variable intervals after initial vaccination with 3 mg protein. Efficacy was confirmed over a year after initial vaccination based on complete ovarian cycle suppression determined by serum progestagen analyses. Estrous cycle suppression was associated with a significant increase in GnRH antibody binding and subsequent decrease in serum luteinizing hormone and follicle-stimulating hormone concentrations. Ultrasonographic examinations of the reproductive tract documented a reduction in uterine size and vascularity after immunization. The hematocrit level normalized soon after the initial intrauterine hemorrhage, and no recurrence of anemia has been detected. No substantive adverse effects were associated with GnRH vaccination. The results indicate that GnRH vaccination in elephants shows potential for contraception and management of uterine pathology in older elephants.

Noninvasive monitoring of adrenocortical function in captive jaguars (Panthera onca).

Jaguars are threatened with extinction throughout their range. A sustainable captive population can serve as a hedge against extinction, but only if they are healthy and reproduce. Understanding how jaguars respond to stressors may help improve the captive environment and enhance their wellbeing. Thus, our objectives were to: (1) conduct an adrenocorticotrophic hormone (ACTH) challenge to validate a cortisol radioimmunoassay (RIA) for noninvasive monitoring of adrenocortical function in jaguars; (2) investigate the relationship between fecal corticoid (FCM) and androgen metabolite (FAM) concentrations in males during the ACTH challenge; and (3) establish a range of physiological concentrations of FCMs for the proposed protocol. Seven jaguars (3 M, 4 F) received 500 IU/animal of ACTH. Pre- and post-ACTH fecal samples were assayed for corticoid (M and F) and androgen metabolites (M) by RIA. Concentrations of FCMs increased (P80.01) after ACTH injection (pre-ACTH: 0.90 ± 0.12 µg/g dry feces; post-ACTH: 2.55 ± 0.25 µg/g). Considering pre- and post-ACTH samples, FCM concentrations were higher (P80.01) in males (2.15 ± 0.20 µg/g) than in females (1.30 ± 0.20 µg/g), but the magnitude of the response to ACTH was comparable (P>0.05) between genders. After ACTH injection, FAMs increased in two (of 3) males; in one male, FCMs and FAMs were positively correlated (0.60; P80.01). Excretion of FCMs was assessed in 16 jaguars (7 M, 9 F) and found to be highly variable (range, 80.11-1.56 µg/g). In conclusion, this study presents a cortisol RIA for monitoring adrenocortical function in jaguars noninvasively.

Lethal iron deprivation induced by non-neutralizing antibodies targeting transferrin receptor 1 in malignant B cells.

A number of antibodies have been developed that induce lethal iron deprivation (LID) by targeting the transferrin receptor 1 (TfR1/CD71) and either neutralizing transferrin (Tf) binding, blocking internalization of the receptor and/or inducing its degradation. We have developed recombinant antibodies targeting human TfR1 (ch128.1 and ch128.1Av), which induce receptor degradation and are cytotoxic to certain malignant B-cells. We now show that internalization of TfR1 bound to these antibodies can lead to its sequestration and degradation, as well as reduced Tf uptake, and the induction of a transcriptional response consistent with iron deprivation, which is mediated in part by downstream targets of p53. Cells resistant to these antibodies do not sequester and degrade TfR1 after internalization of the antibody/receptor complex, and accordingly maintain their ability to internalize Tf. These findings are expected to facilitate the rational design and clinical use of therapeutic agents targeting iron import via TfR1 in hematopoietic malignancies.

Solid crystal network of self-assembled cyclodextrin and nonionic surfactant pseudorotaxanes.

The title system allows the straightforward formation of three-dimensional crystals of self-assembled pseudorotaxanes formed by the nonionic surfactant Igepal CO-520 and beta-cyclodextrin (beta-CD) in aqueous solution. The work involves a combination of X-ray powder diffraction, high resolution electron transmission microscopy, and (13)C CP/MAS NMR studies of the solid crystal, supported by single crystal structural analysis. The results indicate a lamellar self-assembly of pseudorotaxanes with preferential orientation and disorder in the structure. For the single crystal, the unit cell was found to be triclinic (P1) and contains a beta-CD dimer. The surfactant molecules are located in the channel formed by these dimers along the c axis of the crystal network. The individual pseudorotaxane structure is formed by a dimer of beta-CDs threaded by the oxyethylene hydrophilic segment of Igepal CO-520, and a beta-CD dimer that binds the hydrophobic region of the surfactant. Thus, as in a CD polyrotaxane structure, this system results in an ordered self-assembly of pseudorotaxanes through the formation of a network of hydrogen bonds between head-to-head beta-CD dimers. Moreover, the analysis of the (1)H NMR spectra in solutions of pseudorotaxanes formed by beta-CD and Igepals with different lengths of the hydrophilic tails indicates equal stoichiometry patterns of both oxyethyelene and hydrophobic regions for the different supramolecules. Whereas the common hydrophobic moiety threads two macrocycles, the ratio between complexed oxyehtlyene segments and beta-CD is 2.5 for the hydrophilic tails. All these results show that nonionic surfactants can be used as alternative and effective linear threads to polymers and copolymers in the synthesis of supramolecular polyrotaxane solid crystals with CDs.

Reduced right frontal cortical thickness in children, adolescents and adults with ADHD and its correlation to clinical variables: a cross-sectional study.

OBJECTIVE: Some longitudinal magnetic resonance imaging (MRI) studies have shown reduced volume or cortical thickness (CT) in the frontal cortices of individuals with attention-deficit/hyperactivity disorder (ADHD). These studies indicated that the aforementioned anatomical abnormalities disappear during adolescence. In contrast, cross-sectional studies on adults with ADHD have shown anatomical abnormalities in the frontal lobe region. It is not known whether the anatomical abnormalities in ADHD are a delay or a deviation in the encephalic maturation. The aim of this study was to compare CT in the frontal lobe of children, adolescents and adults of both genders presenting ADHD with that in corresponding healthy controls and to explore its relationship with the severity of the illness. METHOD: An MRI scan study was performed on never-medicated ADHD patients. Twenty-one children (6-10 year-olds), twenty adolescents (14-17 year-olds) and twenty adults (25-35 year-olds) were matched with healthy controls according to age and sex. CT measurements were performed using the Freesurfer image analysis suite. RESULTS: The data showed regions in the right superior frontal gyrus where CT was reduced in children, adolescents and adults with ADHD in contrast to their respective healthy controls. The CT of these regions correlated with the severity of the illness. CONCLUSIONS: In subjects with ADHD, there is a thinning of the cortical surface in the right frontal lobe, which is present in the children, adolescents and in adults.