Position preference and diffusion path of an oxygen ion in apatite-type lanthanum silicate La9.33Si6O26: A density functional study

Using density functional theory, we investigated the position preference and diffusion mechanisms of interstitial oxygen ions in lanthanum silicate La9.33Si6O26, which is an apatite-structured oxide and a promising candidate electrolyte material for solid oxide fuel cells. The reported lanthanum vacancies were explicitly taken into account by theoretically determining their arrangement with a supercell model. The most stable structures and the formation energies of oxygen interstitials were determined for each charged state. It was found that the double-negatively charged state is stable over a wide range of the Fermi level, and that the excess oxygen ions form split interstitials with the original oxygen ions, while the neutral and the single-negatively charged states preferably form molecular oxygen. These species were found near the lanthanum vacancy site. The theoretically determined migration pathway along the c-axis essentially follows an interstitialcy mechanism. The obtained migration barrier is sensitive to the charge state, and is also affected by the lanthanum vacancy. The barrier height of the double-negatively charged state was calculated to be 0.58 eV for the model structure, which is consistent with the measured activation energy.

Depressive Disorders in Primary Health Care

The Vantaa Primary Care Depression Study (PC-VDS) is a naturalistic and prospective cohort study concerning primary care patients with depressive disorders. It forms a collaborative research project between the Department of Mental and Alcohol Research of the National Public Health Institute, and the Primary Health Care Organization of the City of Vantaa. The aim is to obtain a comprehensive view on clinically significant depression in primary care, and to compare depressive patients in primary care and in secondary level psychiatric care in terms of clinical characteristics. Consecutive patients (N=1111) in three primary care health centres were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, interview and a retrospective life-chart were used to obtain comprehensive cross-sectional and retrospective longitudinal information. For investigation of suicidal behaviour the Scale for Suicidal Ideation (SSI), patient records and the interview were used. The methodology was designed to be comparable to The Vantaa Depression Study (VDS) conducted in secondary level psychiatric care. Comparison of major depressive disorder (MDD) patients aged 20-59 from primary care in PC-VDS (N=79) was conducted with new psychiatric outpatients (N =223) and inpatients (N =46) in VDS. The PC-VDS cohort was prospectively followed up at 3, 6 and 18 months. Altogether 123 patients (90%) completed the follow-up. Duration of the index episode and the timing of relapses or recurrences were examined using a life-chart. The retrospective investigation revealed current MDD in most (66%), and lifetime MDD in nearly all (90%) cases of clinically significant depressive syndromes. Two thirds of the “subsyndromal” cases had a history of major depressive episode (MDE), although they were currently either in partial remission or a potential prodromal phase. Recurrences and chronicity were common. The picture of depression was complicated by Axis I co-morbidity in 59%, Axis II in 52% and chronic Axis III disorders in 47%; only 12% had no co-morbidity. Within their lifetimes, one third (37%) had seriously considered suicide, and one sixth (17%) had attempted it. Suicidal behaviour clustered in patients with moderate to severe MDD, co-morbidity with personality disorders, and a history of treatment in psychiatric care. The majority had received treatment for depression, but suicidal ideation had mostly remained unrecognised. The comparison of patients with MDD in primary care to those in psychiatric care revealed that the majority of suicidal or psychotic patients were receiving psychiatric treatment, and the patients with the most severe symptoms and functional limitations were hospitalized. In other clinical aspects, patients with MDD in primary care were surprisingly similar to psychiatric outpatients. Mental health contacts earlier in the current MDE were common among primary care patients. The 18-month prospective investigation with a life-chart methodology verified the chronic and recurrent nature of depression in primary care. Only one-quarter of patients with MDD achieved and maintained full remission during the follow-up, while another quarter failed to remit at all. The remaining patients suffered either from residual symptoms or recurrences. While severity of depression was the strongest predictor of recovery, presence of co-morbid substance use disorders, chronic medical illness and cluster C personality disorders all contributed to an adverse outcome. In clinical decision making, beside severity of depression and co-morbidity, history of previous MDD should not be ignored by primary care doctors while depression there is usually severe enough to indicate at least follow-up, and concerning those with residual symptoms, evaluation of their current treatment. Moreover, recognition of suicidal behaviour among depressed patients should also be improved. In order to improve outcome of depression in primary care, the often chronic and recurrent nature of depression should be taken into account in organizing the care. According to literature management programs of a chronic disease, with enhancement of the role of case managers and greater integration of primary and specialist care, have been successful. Optimum ways of allocating resources between treatment providers as well as within health centres should be found.

Cyclic AMP in Mycobacteria: Characterization and Functional Role of the Rv1647 Ortholog in Mycobacterium smegmatis{triangledown}

Mycobacterial genomes are endowed with many eukaryote-like nucleotide cyclase genes encoding proteins that can synthesize 3',5'-cyclic AMP (cAMP). However, the roles of cAMP and the need for such redundancy in terms of adenylyl cyclase genes remain unknown. We measured cAMP levels in Mycobacterium smegmatis during growth and under various stress conditions and report the first biochemical and functional characterization of the MSMEG_3780 adenylyl cyclase, whose orthologs in Mycobacterium tuberculosis (Rv1647) and Mycobacterium leprae (ML1399) have been recently characterized in vitro. MSMEG_3780 was important for producing cAMP levels in the logarithmic phase of growth, since the {Delta}MSMEG_3780 strain showed lower intracellular cAMP levels at this stage of growth. cAMP levels decreased in wild-type M. smegmatis under conditions of acid stress but not in the {Delta}MSMEG_3780 strain. This was correlated with a reduction in MSMEG_3780 promoter activity, indicating that the effect of the reduction in cAMP levels on acid stress was caused by a decrease in the transcription of MSMEG_3780. Complementation of the {Delta}MSMEG_3780 strain with the genomic integration of MSMEG_3780 or the Rv1647 gene could restore cAMP levels during logarithmic growth. The Rv1647 promoter was also acid sensitive, emphasizing the biochemical and functional similarities in these two adenylyl cyclases. This study therefore represents the first detailed biochemical and functional analysis of an adenylyl cyclase that is important for maintaining cAMP levels in mycobacteria and underscores the subtle roles that these genes may play in the physiology of the organism.

Heritability of the network architecture of intrinsic brain functional connectivity

The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and "rich-club" properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5-25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23±2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h2 (γ=47-59%, Q=38-59%, ϕnorm=0-29%, λ=52-64%, σ=51-59%) at lower connection densities (≤15%), and when global signal regression was implemented, heritability estimates decreased substantially h2 (γ=0-26%, Q=0-28%, ϕnorm=0%, λ=23-30%, σ=0-27%). Distinct network features were phenotypically correlated (|r|=0.15-0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices.

Seeing and hearing speech, sounds, and signs: functional magnetic resonance studies on fluent and dyslexic readers

Speech has both auditory and visual components (heard speech sounds and seen articulatory gestures). During all perception, selective attention facilitates efficient information processing and enables concentration on high-priority stimuli. Auditory and visual sensory systems interact at multiple processing levels during speech perception and, further, the classical motor speech regions seem also to participate in speech perception. Auditory, visual, and motor-articulatory processes may thus work in parallel during speech perception, their use possibly depending on the information available and the individual characteristics of the observer. Because of their subtle speech perception difficulties possibly stemming from disturbances at elemental levels of sensory processing, dyslexic readers may rely more on motor-articulatory speech perception strategies than do fluent readers. This thesis aimed to investigate the neural mechanisms of speech perception and selective attention in fluent and dyslexic readers. We conducted four functional magnetic resonance imaging experiments, during which subjects perceived articulatory gestures, speech sounds, and other auditory and visual stimuli. Gradient echo-planar images depicting blood oxygenation level-dependent contrast were acquired during stimulus presentation to indirectly measure brain hemodynamic activation. Lip-reading activated the primary auditory cortex, and selective attention to visual speech gestures enhanced activity within the left secondary auditory cortex. Attention to non-speech sounds enhanced auditory cortex activity bilaterally; this effect showed modulation by sound presentation rate. A comparison between fluent and dyslexic readers' brain hemodynamic activity during audiovisual speech perception revealed stronger activation of predominantly motor speech areas in dyslexic readers during a contrast test that allowed exploration of the processing of phonetic features extracted from auditory and visual speech. The results show that visual speech perception modulates hemodynamic activity within auditory cortex areas once considered unimodal, and suggest that the left secondary auditory cortex specifically participates in extracting the linguistic content of seen articulatory gestures. They are strong evidence for the importance of attention as a modulator of auditory cortex function during both sound processing and visual speech perception, and point out the nature of attention as an interactive process (influenced by stimulus-driven effects). Further, they suggest heightened reliance on motor-articulatory and visual speech perception strategies among dyslexic readers, possibly compensating for their auditory speech perception difficulties.

Investigation of dye functional group on the photocatalytic degradation of dyes by nano-TiO2

The photocatalytic degradation of five anionic, eight cationic and three solvent dyes using combustion-synthesized nano-TiO2 (CSTiO2) and commercial Degussa P-25 TiO2 (DP-25) were evaluated to determine the effect of the functional group in the dye. The degradation of the dyes was quantified using the initial rate of decolorization and mineralization. The decolorization of the anionic dyes with CSTiO2 followed the order: indigo carmine > eosin Y > amido black 10B > alizarin cyanine green > orange G. The decolorization of the cationic dyes with DP-25 followed the order: malachite green > pyronin Y > rhodamine 6G > azure B > nile blue sulfate > auramine O approximate to acriflavine P approximate to safranin O. CSTiO2 showed higher rates of decolorization and mineralization for all the anionic dyes compared to DP-25, while DP-25 was better in terms of decolorization for most of the cationic dyes. The solvent dyes exhibited adsorption dependent decolorization. The order of decolorization and mineralization of the anionic and cationic dyes (a) with CS TiO2 and DP-25 was different and correlated with the surface properties of these catalysts (b) were rationalized with the molecular structure of the dye and the degradation pathway of the dye. (C) 2009 Elsevier B.V. All rights reserved.

Functional interaction of diphenols with polyphenol oxidase - Molecular determinants of substrate/inhibitor specificity SO FEBS JOURNAL

Polyphenol oxidase (PPO) catalyzes the oxidation of o-diphenols to their respective quinones. The quinones autopolymerize to form dark pigments, an undesired effect. PPO is therefore the target for the development of antibrowning and antimelanization agents. A series of phenolic compounds experimentally evaluated for their binding affinity and inhibition constants were computationally docked to the active site of catechol oxidase. Docking studies suggested two distinct modes of binding, dividing the docked ligands into two groups. Remarkably, the first group corresponds to ligands determined to be substrates and the second group corresponds to reversible inhibitors. Analyses of the complexes provide structural explanations for correlating subtle changes in the position and nature of the substitutions on o-diphenols to their functional properties as substrates and inhibitors. Higher reaction rates and binding are reckoned by additional interactions of the substrates with key residues that line the hydrophobic cavity. The docking results suggest that inhibition of oxidation stems from an interaction between the aromatic carboxylic acid group and the apical His 109 of the four coordinates of the trigonal pyramidal coordination polyhedron of CuA. The spatial orientation of the hydroxyl in relation to the carboxylic group either allows a perfect fit in the substrate cavity, leading to inhibition, or because of a steric clash flips the molecule vertically, facilitating oxidation. This is the first study to explain, at the molecular level, the determinants Of substrate and inhibitor specificity of a catechol oxidase, thereby providing a platform for the design of selective inhibitors useful to both the food and pharmaceutical industries.

Microvascular reconstruction in extremity soft tissue sarcoma surgery

Soft tissue sarcomas (STS) are rare tumors of soft tissue occurring most frequently in the extremities. Modern treatment of extremity STS is based on limb-sparing surgery combined with radiotherapy. To prevent local recurrence, a healthy tissue margin of 2.5 cm around the resected tumor is required. This results in large defects of soft tissue and bone, necessitating the use of reconstructive surgery to achieve wound closure. When local or pedicled soft tissue flaps are unavailable, reconstruction with free flaps is used. Free flaps are elevated at a distant site, and have their blood flow restored at the recipient site through microvascular anastomosis. When limb-sparing surgery is made impossible, amputation is the only option. Proximal amputation such as forequarter amputation (FQA) causes considerable morbidity, but is nevertheless warranted for carefully selected patients for cure or palliation. 116 patients treated in 1985 - 2006 were included in the study. Of these, 93 patients treated with limb-sparing surgery and microvascular reconstructive surgery after resection of extremity STS. 25 patients who underwent FQA were also included. Patients were identified and their medical records retrospectively reviewed. In all, 105 free flap procedures were performed for 103 patients. A total of 95 curatively treated STS patients were included in survival analysis. The latissimus dorsi, used in 56% of cases, was the most frequently used free flap. Free flap success rate was 96%. There were 9% microvascular anastomosis complications and 15% wound complications. For curatively treated STS patients, local recurrence-free survival at 5 years was 73.1%, metastasis-free survival 58.3%, and overall disease-specific survival 68.9%. Functional results were good, with 75% of patients regaining normal or near-normal function after lower extremity, and 55% after upper extremity STS resection. Among curatively treated forequarter amputees, 5-year disease-free survival was 44%. In the palliatively treated group median time until disease death was 14 months. Microvascular reconstruction after extremity soft tissue sarcoma resection is safe and reliable, and produces well-healing wounds allowing early oncological treatment. Oncological outcome after these procedures is comparable to that of other extremity sarcoma patients. Functional results are generally good. Forequarter amputation is a useful treatment option for soft tissue tumors of the shoulder girdle and proximal upper extremity. When free flap coverage of extended forequarter amputation is required, the preferable flap is a fillet flap from the amputated extremity. Acceptable oncological outcome is achieved for curatively treated FQA patients. In the palliatively treated patient considerable periods of increased quality of life can be achieved.

Inferring molecular function: contributions from functional linkages

In the current era of high-throughput sequencing and structure determination, functional annotation has become a bottleneck in biomedical science. Here, we show that automated inference of molecular function using functional linkages among genes increases the accuracy of functional assignments by >= 8% and enriches functional descriptions in >= 34% of top assignments. Furthermore, biochemical literature supports >80% of automated inferences for previously unannotated proteins. These results emphasize the benefit of incorporating functional linkages in protein annotation.

Evaluating the effectiveness of a self-management exercise intervention on wound healing, functional ability and health-related quality of life outcomes in adults with venous leg ulcers: a randomised controlled trial

Exercise that targets ankle joint mobility may lead to improvement in calf muscle pump function and subsequent healing. The objectives of this research were to assess the impact of an exercise intervention in addition to routine evidence-based care on the healing rates, functional ability and health-related quality of life for adults with venous leg ulcers (VLUs). This study included 63 patients with VLUs. Patients were randomised to receive either a 12-week exercise intervention with a telephone coaching component or usual care plus telephone calls at the same timepoints. The primary outcome evaluated the effectiveness of the intervention in relation to wound healing. The secondary outcomes evaluated physical activity, functional ability and health-related quality of life measures between groups at the end of the 12 weeks. A per protocol analysis complemented the effectiveness (intention-to-treat) analysis to highlight the importance of adherence to an exercise intervention. Intention-to-treat analyses for the primary outcome showed 77% of those in the intervention group healed by 12 weeks compared to 53% of those in the usual care group. Although this difference was not statistically significant due to a smaller than expected sample size, a 24% difference in healing rates could be considered clinically significant. The per protocol analysis for wound healing, however, showed that those in the intervention group who adhered to the exercise protocol 75% or more of the time were significantly more likely to heal and showed higher rates for wound healing than the control group (P = 0·01), that is, 95% of those who adhered in the intervention group healed in 12 weeks. The secondary outcomes of physical activity, functional ability and health-related quality of life were not significantly altered by the intervention. Among the secondary outcomes (physical activity, functional ability and health-related quality of life), intention-to-treat analyses did not support the effectiveness of the intervention. However, per protocol analyses revealed encouraging results with those participants who adhered more than 75% of the time (n = 19) showing significantly improved Range of Ankle Motion from the self-management exercise programme (P = 0·045). This study has shown that those participants who adhere to the exercise programme as an adjunctive treatment to standard care are more likely to heal and have better functional outcomes than those who do not adhere to the exercises in conjunction with usual care.

Functional characterization of lysophosphatidic acid phosphatase from Arabidopsis thaliana

Lysophosphatidic acid (LPA) acts as a signaling molecule that regulates diverse cellular processes and it can rapidly be metabolized by phosphatase and acyltransferase LPA phosphatase gene has not been identified and characterized in plants so far The BLAST search revealed that the At3g03520 is similar to phospholipase family. and distantly related to bacterial phosphatases The conserved motif. (J)4XXXNXSFD, was identified in both At3g03520 like phospholipases and acid phosphatases In silico expression analysis of At3g03520 revealed a high expression during phosphate starvation and abiotic stresses. This gene was overexpressed in Escherichia coli and shown to posses LPA specific phosphatase activity These results Suggest that this gene possibly plays a role in signal transduction and storage lipid synthesis.