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An unexpected discovery of two interferon gamma-like genes along with interleukin (IL)-22 and -26 from teleost: IL-22 and -26 genes have been described for the first time outside mammals.

By comparative genomics based on chromosome synteny between human and fish, IL-22, IL-26 and two IFN-gamma-like genes have been isolated in fish. Interleukin-22 and -26 have been identified for the first time outside of mammals and their organization and synteny demonstrates that this cluster of cytokines is well conserved during evolution. The cloned zebrafish IL-22 and -26 homologs are 161 and 169-aa long, respectively. Both the genes harbor a well-conserved IL-10-family signature in their respective C-terminus. The coding regions of these genes are spread in five exons and at the same position as in human homologs. Furthermore, surprisingly two IFN-gamma-like genes are present in tandem, 7.0 kb apart from each other, along this locus. IFN-gamma1 and 2 genes are composed of 170- and 185-aa and share a low amino acid identity of 17.0%. The genomic structures of the isolated fish IFN-gamma genes were similar to its mammalian homologs, sharing a four exon and three phase 0 introns. The presence two IFN-gamma genes in both zebra and pufferfishes demonstrate that the duplication of IFN-gamma might have occurred prior to the teleostean split. The structural homology is further validated by phylogenetic analysis showing that the isolated cytokine genes are homologous to mammalian counterparts. Expression analysis of IL-22, IL-26 and two IFN-gamma genes suggests an active role of these genes in immune responses in fish.

Amino Acid Sequence↗

MRI as a key tool for understanding and modeling the filtration kinetics of fibrous media.

Applying MRI techniques to low-density fibrous filter media provides us with unique information about the initial structure and deposited mass within the same filter sample. This now enables us to obtain the necessary link between structure and deposition for validation and further enhancement of modeling filtration kinetics. However, additional work is needed before achieving a realistic understanding of filtration kinetics.

Filtration↗

Independent component analysis of fMRI group studies by self-organizing clustering.

Independent component analysis (ICA) is a valuable technique for the multivariate data-driven analysis of functional magnetic resonance imaging (fMRI) data sets. Applications of ICA have been developed mainly for single subject studies, although different solutions for group studies have been proposed. These approaches combine data sets from multiple subjects into a single aggregate data set before ICA estimation and, thus, require some additional assumptions about the separability across subjects of group independent components. Here, we exploit the application of similarity measures and a related visual tool to study the natural self-organizing clustering of many independent components from multiple individual data sets in the subject space. Our proposed framework flexibly enables multiple criteria for the generation of group independent components and their random-effects evaluation. We present real visual activation fMRI data from two experiments, with different spatiotemporal structures, and demonstrate the validity of this framework for a blind extraction and selection of meaningful activity and functional connectivity group patterns. Our approach is either alternative or complementary to the group ICA of aggregated data sets in that it exploits commonalities across multiple subject-specific patterns, while addressing as much as possible of the intersubject variability of the measured responses. This property is particularly of interest for a blind group and subgroup pattern extraction and selection.

Adult↗

Genetic Landscape of Opsoclonus-Myoclonus-Ataxia Syndrome in Children.

BACKGROUND: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare neurological disorder, with involuntary rapid saccadic conjugate eye movements as one of characteristics, primarily affecting the cerebellum. While the exact pathogenesis remains unclear, genetic and autoimmune factors have been suggested to contribute to its development. METHODS: We enrolled patients diagnosed with OMAS before the age of 18 years at a pediatric neuroimmunology clinic in Boston, United States, using the 2004 Genoa Criteria. Whole genome sequencing was conducted for the patients and their biological parents in all cases, with one case including an unaffected twin sibling. RESULTS: De novo germline variants (DNVs) in probands were identified and validated and analyses of structural variants, recessive variants in neuroimmune-associated genes, and high-resolution human leukocyte antigen (HLA) typing were performed. Our study included 42 patients, 23 of whom had neuroblastoma. We found 12 confirmed DNVs in protein-coding regions in nine patients (29.0% of 31 from 30 trios and 1 quartet). Ten patients (23.8% of 42) had rare homozygous or compound heterozygous variants known to alter protein function, affecting 11 genes. Notably, the major histocompatibility complex, class II, DR beta 1 (HLA-DRB1) &#x2217;01 allele was observed in 27 out of 84 (32.1%) alleles in the patients, significantly higher than that in the general population (chi-square test, P < 0.0001). In one case, a potential genetic modifier of OMAS with severe cerebellar atrophy was identified, associated with a protein-truncating DNV in the CACNA2D2 gene. CONCLUSIONS: This first genome sequencing study reveals potential genetic contributors to OMAS, implicating polygenic predisposition-with HLA-DRB1&#x2217;01 as a possible factor-combined with nongenetic risk factors like neuroblastoma.

Humans↗

Incremental geriatric assessment.

Older adults value (1) independence and the ability to make their own decisions, (2) mobility (the ability to travel outside or simply inside the home), (3) family and friends and the time spent with those persons who are important to them, (4) ethnicity, religion, and spirituality, and (5) home, wherever that might be. The importance of recognizing each person's individuality cannot be overemphasized. The method of incremental assessment presented in this article and summarized in Box 9 is intended to provide the office-based clinician with sufficient information to make decisions regarding the preventive, therapeutic, rehabilitative, and supportive goals of care. IADL and nutritional triggers are used to identify early signs of dysfunction in the home environment. The strengths and weaknesses of cognitive, physical, psychosocial, and spiritual aspects of function are examined in an incremental manner. Health care providers determine whether there is a match between the person's functional capabilities, the available support network, and the home environment. The approach prompts appropriate use of services needed by older adults who are either at risk for becoming, or already are, chronically ill, disabled, and functionally dependent. Use of validated assessment tools provides structure for the assessment process, helps assure consistency, and provides a mechanism for periodic re-evaluation. The assessment approaches also foster a common language for the health care team and consist of measurable parameters that can be used to monitor outcomes. The clinician should be flexible and realize that the assessment or the tools may need to be modified depending on the circumstances.

Activities of Daily Living↗

Modeling the effect of inbreeding among founders in linkage analysis.

In this paper, we present a unified mathematical model for linkage analysis that allows for inbreeding among founders in all families. The identical by descent (IBD) configuration of each pedigree is modeled as a Markov process containing two parameters; the inverse inbreeding and kinship coefficient and a rate parameter proportional to the inverse expected length of chromosome segments shared IBD by two different founder haplotypes. We use hidden Markov models and define a forward-backward algorithm for computing the conditional IBD-distribution given marker data, thereby extending the multipoint method of Lander and Green [1987. Construction of multilocus genetic maps in humans, Proc. Natl. Acad. Sci. USA 84, 2363-2367] to situations where founders are inbred. Our methodology is valid for arbitrary pedigree structures. Simulation and theoretical approximations for nonparametric linkage (NPL) analysis based on affected sib pairs reveal that NPL scores are inflated and type 1 errors increased when the inbreeding coefficient or rate parameter is underestimated. When the parents are genotyped, we present a general way of modifying the score function to drastically reduce this effect.

Algorithms↗

Cross-sectional assessment of psychiatric disorders in renal transplantation patients in Turkey: a preliminary study.

BACKGROUND: Psychiatric disorders such as depression and anxiety may be seen after a successful renal transplantation (RTx). The aim of this cross-sectional study was the assessment of psychiatric disorders after RTx in Turkey. The value of self-report scales in predicting depression and anxiety was also assessed. PATIENTS AND METHODS: The study group consisted of 20 male and 20 female RTx patients (mean age 35.42 +/- 10.09 years), with a mean duration of 61.65 +/- 48.30 months of follow-up after transplantation. All patients were assessed with the validated Turkish versions of Structured Clinical Interview for the DSM-IV (SCID-I), Beck Depression Inventory (BDI), Hospital Anxiety Depression Scales (HADS), Spielberger Trait Anxiety Inventory (STAI-I), and Beck Hopelessness Scale (BHS). RESULTS: Twenty of the 40 patients warranted a DSM-IV psychiatric diagnosis with SCID-I evaluation. Major depression was observed in 25% of patients. The remaining diagnoses were within the affective and/or anxiety spectrum disorders. The set of age, gender, education, income, marital status, employment, type of transplantation, duration of illness, and duration after the transplantation was not significantly different between patients with or without psychiatric diagnoses. BDI, HADS, STAI-I, and BHS were significantly higher among patients with psychiatric diagnoses at P = .001 level using Student t test. Even after control of the variance explained by the set of demographic variables, hierarchical regression analysis revealed that HADS scores significantly predicted the psychiatric morbidity (P = .003). CONCLUSION: The frequency of psychiatric disorders is quite high in renal transplantation patients. Additionally, HADS, which significantly predicts depression and anxiety, may be used for screening purposes.

Adolescent↗

Complexity management theory: motivation for ideological rigidity and social conflict.

We are doomed to formulate conceptual structures that are much simpler than the complex phenomena they are attempting to account for. These simple conceptual structures shield us, pragmatically, from real-world complexity, but also fail, frequently, as some aspect of what we did not take into consideration makes itself manifest. The failure of our concepts dysregulates our emotions and generates anxiety, necessarily, as the unconstrained world is challenging and dangerous. Such dysregulation can turn us into rigid, totalitarian dogmatists, as we strive to maintain the structure of our no longer valid beliefs. Alternatively, we can face the underlying complexity of experience, voluntarily, gather new information, and recast and reconfigure the structures that underly our habitable worlds.

Amygdala↗

Immuno-purification of a dimeric subcomplex of the respiratory NADH-CoQ reductase of Rhodobacter capsulatus equivalent to the FP fraction of the mitochondrial complex I.

The Rhodobacter capsulatus genes encoding the NUOE and NUOF subunits, equivalent to the 24 kDa and 51 kDa subunits of the mammalian mitochondrial complex I, have been sequenced. According to the nucleotide sequence, the NUOE subunit is 389 amino acids long and has a molecular mass of 41.3 kDa. In comparison to the mitochondrial equivalent subunit, NUOE is extended at the C terminus by more than 150 amino acids. The NUOF subunit is 431 amino acids long and has a molecular mass of 47.1 kDa. A subcomplex containing both the NUOE and NUOF subunits was extracted by detergent treatment of R. capsulatus membranes and immuno-purified. This subcomplex is homologous to the mitochondrial FP fragment. Mass spectrometry after trypsin treatment of the NUOE subunit validates the atypical primary structure deduced from the sequence of the gene.

Amino Acid Sequence↗

Non-linear qualitative signal processing for biological systems: application to the algal growth in bioreactors.

We present in this paper a qualitative method to validate and monitor the structure of a non-linear model with respect to experimental data, under some hypotheses. This method is broadly independent of the analytical formulation of the model, and depends only on the qualitative structure (the signs of the Jacobian matrix). The temporal sequences of the extrema of a filtered experimental signal are compared with the transitions allowed by a graph. In particular, we show that the usual moving average of the outputs follows this transition graph. We apply this method to compare models of algal growth in a bioreactor with experimental data.

Bioreactors↗

The organization of central cholinergic systems and their functional importance in sleep-waking states.

Since the demonstration some 50 years ago of the presence and synthesis of acetylcholine (ACh) in specific neuronal systems within the brain, a wealth of information concerning the organization and functional importance of central cholinergic neurons has emerged through immunohistochemical, neuroanatomical, pharmacological, biochemical and neurophysiological studies. Many of the original theses have proven valid concerning the key structural and functional position of cholinergic neurons within the central reticular core of the brain, where the basic sleep-waking cycle is determined. The two major cholinergic cell groups of this core, one within the pontomesencephalic tegmentum that projects rostrally into the non-specific thalamo-cortical relay system and the other within the basal forebrain that receives input from the brainstem reticular formation and projects in turn as the ventral, extrathalamic relay upon the cerebral cortex, are critically involved in processes of cerebral activation that accompany the states of wakefulness and paradoxical sleep. By interaction with other cell groups, including monoaminergic and GABAergic neurons, and by differential modes of firing, the cholinergic neurons may furthermore shape the responsiveness and activity of the reticular core and thalamo-cortical systems across the sleep-waking cycle.

Acetylcholine↗

Functional interaction of cytochrome P450 with its redox partners: a critical assessment and update of the topology of predicted contact regions.

The problem of donor-acceptor recognition has been the most important and intriguing one in the area of P450 research. The present review outlines the topological background of electron-transfer complex formation, showing that the progress in collaborative investigations, combining physical techniques with chemical-modification and immunolocalization studies as well as site-directed mutagenesis experiments, has increasingly enabled the substantiation of hypothetical work resulting from homology modelling of P450s. Circumstantial analysis reveals the contact regions for redox proteins to cluster on the proximal face of P450s, constituting parts of the highly conserved, heme-binding core fold. However, more variable structural components located in the periphery of the hemoprotein molecules also participate in donor docking. The cross-reactivity of electron carriers, purified from pro- and eukaryotic sources, with a diversity of P450 species points at a possible evolutionary conservation of common anchoring domains. While electrostatic mechanisms appear to dominate orientation toward each other of the redox partners to generate pre-collisional encounter complexes, hydrophobic forces are likely to foster electron transfer events by through-bonding or pi-stacking interactions. Moreover, electron-tunneling pathways seem to be operative as well. The availability of new P450 crystal structures together with improved validation strategies will undoubtedly permit the production of increasingly satisfactory three-dimensional donor-acceptor models serving to better understand the molecular principles governing functional association of the redox proteins.

Animals↗

Analysis of the psychometric properties of the Spanish version of the Beck Depression Inventory in Argentina.

Increased international collaboration in clinical trials has created a need for cross-culturally valid instruments to assess quality of life and behavioral disorders. Cross-cultural studies of depressive symptomatology, in particular, must be preceded by an exhaustive study of the psychometric properties of the instruments, to ensure the validity of the comparison. In this article, we examine the validity, reliability and factor structure of the Spanish version of the Beck Depression Inventory (BDI) in a random stratified sample of 608 community residents in Argentina. Our findings indicate that this version of the BDI is psychometrically strong and appropriate for use in Argentina, and we suggest that it is suitable for assessing depressive symptomatology in Spanish speakers.

Adult↗

Validation of protein-based alignment in 3D quantitative structure-activity relationships with CoMFA models.

The predictive capabilities of protein-based alignment (PBA) and structure-based alignment (SBA) comparative molecular field analysis (CoMFA) models have been compared. 3D quantitative structure-activity relationship (3D QSAR) models have been derived for a series of N-benzylpiperidine derivatives which are potent acetylcholinesterase (AChE) inhibitors interesting for Alzheimer's disease. To establish a comparison with the classical SBA procedure, different assay models were derived by superposing ligand conformers that are docked to the AChE active site and by using the most active compound as the reference one. A Kohonen self organizing map (SOM) was applied to analyse the molecular diversity of the test set relative to that of the training set, in order to explain the influence of molecular diversity on the predictive power of the considered models. SBA 3D QSAR models have to be used to predict the inhibitory activity only for compounds belonging to subgroups included in the training set. The PBA 3D QSAR models appeared to have a higher predictability, even for compounds with a molecular diversity greater than that of the training set. This results from the fact that the protein helps to automatically select the active conformation which is fitting the 3D QSAR model.

Acetylcholinesterase↗

Validity of the longitudinal, expert, all data procedure for psychiatric diagnosis in patients with psychoactive substance use disorders.

The longitudinal, expert, all data (LEAD) procedure has been employed as a criterion for the assessment of the procedural validity of diagnostic instruments. This study evaluated the procedure's concurrent, discriminant and predictive validity. Interview and questionnaire data obtained from 100 individuals in a substance abuse treatment program were used to assess current and lifetime substance use disorders and common comorbid disorders. An experienced, doctoral-level clinician formulated LEAD diagnoses for each patient, based on an initial interview, ongoing clinical contact and the results of the research assessment and all available clinical records. LEAD-derived substance use diagnoses showed good concurrent, discriminant and predictive validity. The validity of comorbid diagnoses obtained using the LEAD procedure was generally fair to good. Comparison with diagnoses based only on the clinician's unstructured initial interview showed that the availability of additional data enhanced diagnostic validity. Diagnoses derived by a research technician using the Structured Clinical Interview for DSM-III-R showed validity comparable to that of LEAD diagnoses. To enhance its diagnostic validity, applications of the LEAD standard should include a structured interview. Other variations in the application of the LEAD standard, including a longer evaluation period, may also enhance its performance as a diagnostic criterion measure.

Adult↗

Measuring psychiatric disorder among Southeast Asian refugees.

Four measures of mental health--Panic, Depression, Somatization and Well-Being--have been developed for use in a population of Southeast Asian refugees. The scales, a product of work with 1348 refugees, demonstrate conceptual significance, good reliability, concurrent validity and stability of structure across samples. They are culturally sensitive, enabling intra-cultural study as well as screening for clinical purposes. The measures also permit comparisons, for research purposes, with non-Asians.

Adaptation, Psychological↗

Application of countercurrent chromatography/thermospray mass spectrometry for the identification of bioactive lignans from plant natural products.

The versatility and resolving power of countercurrent chromatography (CCC) has been demonstrated with a newly developed analytical high-speed planet centrifuge system. Interfacing countercurrent chromatography with mass spectrometry (MS) provides a new analytical methodology that integrates the advantages of countercurrent chromatography with the low detection limit and identification capability of mass spectrometry. In this paper the capability of thermospray CCC/MS is demonstrated in identifying and validating the bioactive and structurally known lignans from a crude extract of Schisandra rubriflora Rhed et Wils, a traditional Chinese herbal medicine for treatment of hepatitis.

Chromatography↗

A correlation for the pressure drop in monolithic silica columns.

To gain insight into how the pressure drop in monolithic silica columns is determined by the microscopic details of the pore structure, a series of well-validated computational fluid dynamics simulations has been performed on a simplified model structure, the so-called tetrahedral skeleton column. From these simulations, a direct correlation between the pressure drop and two main structural properties (skeleton thickness and column porosity) of the monolithic skeleton could be established. The correlation shows good agreement with the experimental pressure-drop data available from the literature on silica monoliths, especially when a correction for the flow-through pore size heterogeneity is made. The established correlation also yields a much more accurate representation of the relation between the flow resistance and the bed porosity than does the Kozeny-Carman model, making it much better suited for porosity optimization calculations.

Journal Article↗