Self-assembly of a designed amyloid peptide containing the functional thienylalanine unit

The self-assembly of a peptide based on a sequence from the amyloid beta peptide but incorporating the non-natural amino acid beta-2-thienylalanine (2-Thi) has been investigated in aqueous and methanol solutions. The peptide AAKLVFF was used as a design motif, replacing the phenylalanine residues (F) with 2-Thi units to yield (2-Thi)(2-Thi)VLKAA. The 2-Thi residues are expected to confer interesting electronic properties due to charge delocalization and pi-stacking. The peptide is shown to form beta-sheet-rich amyloid fibrils with a twisted morphology, in both water and methanol solutions at sufficiently high concentration. The formation of a self-assembling hydrogel is observed at high concentration. Detailed molecular modeling using molecular dynamics methods was performed using NOE constraints provided by 2D-NMR experiments. The conformational and charge properties of 2-Thi were modeled using quantum mechanical methods, and found to be similar to those previously reported for the beta-3-thienylalanine analogue. The molecular dynamics simulations reveal well-defined folded structures (turn-like) in dilute aqueous solution, driven by self-assembly of the hydrophobic aromatic units, with charged lysine groups exposed to water.

Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato–thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto–striato–parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto–striato–cerebellar dysregulation in ASD.

Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers

Studies have revealed abnormalities in resting-state functional connectivity in those with major depressive disorder specifically in areas such as the dorsal anterior cingulate, thalamus, amygdala, the pallidostriatum and subgenual cingulate. However, the effect of antidepressant medications on human brain function is less clear and the effect of these drugs on resting-state functional connectivity is unknown. Forty volunteers matched for age and gender with no previous psychiatric history received either citalopram (SSRI; selective serotonergic reuptake inhibitor), reboxetine (SNRI; selective noradrenergic reuptake inhibitor) or placebo for 7 days in a double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected the right nucleus accumbens, the right amygdala, the subgenual cingulate and the dorsal medial prefrontal cortex as seed regions. Mood and subjective experience were also measured before and after drug administration using self-report scales. Despite no differences in mood across the three groups, we found reduced connectivity between the amygdala and the ventral medial prefrontal cortex in the citalopram group and the amygdala and the orbitofrontal cortex for the reboxetine group. We also found reduced striatal-orbitofrontal cortex connectivity in the reboxetine group. These data suggest that antidepressant medications can decrease resting-state functional connectivity independent of mood change and in areas known to mediate reward and emotional processing in the brain. We conclude that hypothesis-driven seed based analysis of resting-state fMRI supports the proposition that antidepressant medications might work by normalising the elevated resting-state functional connectivity seen in depressed patients.

Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology.

Functional identity and diversity of animals predict ecosystem functioning better than species-based indices

Drastic biodiversity declines have raised concerns about the deterioration of ecosystem functions and have motivated much recent research on the relationship between species diversity and ecosystem functioning. A functional trait framework has been proposed to improve the mechanistic understanding of this relationship, but this has rarely been tested for organisms other than plants. We analysed eight datasets, including five animal groups, to examine how well a trait-based approach, compared with a more traditional taxonomic approach, predicts seven ecosystem functions below- and above-ground. Trait-based indices consistently provided greater explanatory power than species richness or abundance. The frequency distributions of single or multiple traits in the community were the best predictors of ecosystem functioning. This implies that the ecosystem functions we investigated were underpinned by the combination of trait identities (i.e. single-trait indices) and trait complementarity (i.e. multi-trait indices) in the communities. Our study provides new insights into the general mechanisms that link biodiversity to ecosystem functioning in natural animal communities and suggests that the observed responses were due to the identity and dominance patterns of the trait composition rather than the number or abundance of species per se.

Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder

Objective: Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions in BD. Methods: Thirty-three individuals with BD and 31 healthy comparison subjects (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results: Functional connectivity was decreased between the pACC and amygdala in the BD group compared with HC group, during the processing of fearful and happy faces (p < .005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter, including the region of the uncinate fasciculus, was identified (p < .005). Conclusion: This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Trypanosoma cruzi MSH2: Functional analyses on different parasite strains provide evidences for a role on the oxidative stress response

Components of the DNA mismatch repair (MMR) pathway are major players in processes known to generate genetic diversity, such as mutagenesis and DNA recombination. Trypanosoma cruzi, the protozoan parasite that causes Chagas disease has a highly heterogeneous population, composed of a pool of strains with distinct characteristics. Studies with a number of molecular markers identified up to six groups in the T. cruzi population, which showed distinct levels of genetic variability. To investigate the molecular basis for such differences, we analyzed the T. cruzi MSH2 gene, which encodes a key component of MMR, and showed the existence of distinct isoforms of this protein. Here we compared cell survival rates after exposure to genotoxic agents and levels of oxidative stress-induced DNA in different parasite strains. Analyses of msh2 mutants in both T. cruzi and T. brucei were also used to investigate the role of Tcmsh2 in the response to various DNA damaging agents. The results suggest that the distinct MSH2 isoforms have differences in their activity. More importantly, they also indicate that, in addition to its role in MMR, TcMSH2 acts in the parasite response to oxidative stress through a novel mitochondrial function that may be conserved in T. brucei. (C) 2010 Elsevier B.V. All rights reserved.

Perceptions of Sustainability and Functional Aspects on Liquid Carton Board Packaging Materials versus Competing Materials for Juice Applications in Sweden

This research explores the downstream perceptions of liquid carton board versus competing materials in packaging applications for juice. The methodology used is focus groups. The context is sustainability and functional performance, and related potential implications for the beverage industry value chain. The purpose is to get a deeper insight and understanding of functionality in relation to juice beverage packaging. The results confirm that there is no optimal packaging for every juice product, but a multitude, depending on the distribution channel, retail outlet, customer preferences, and context of consumption. There are some general packaging preferences, but the main deciding criteria for purchase seem to be the product characteristics in terms of quality, taste, brand, price and shelf life. For marketing reasons, packaging has to be adopted to the product and its positioning, liquid carton board packaging seem to have some functional advantages in distribution and is considered as sustainable and functional among many consumers. Major drawbacks seem to be shape limitations, lack of transparency, and lack of a “premium look”. To improve packaging performance and avoid sub-optimization, actors in the beverage industry value chain need to be integrated in development processes.

Clinical evaluation of enalapril maleate and furosemide usage in dogs with degenerative myxomatous mitral valve, CHF functional class Ib

A doença degenerativa mixomatosa da válvula mitral (DDMVM) é uma cardiopatia de alta incidência na clínica médica de pequenos animais, acometendo mormente cães idosos e raças de pequeno porte. Desta forma, foi realizada uma investigação científica objetivando avaliar clinicamente a utilização dos fármacos maleato de enalapril e furosemida em cães com a referida enfermidade na classe funcional Ib da ICC, antes e após a terapêutica implantada. Para isso, utilizaram-se 16 cães portadores da valvulopatia supracitada, distribuídos em dois grupos; com o primeiro recebendo furosemida (n=8) e o segundo maleato de enalapril (n=8), durante 56 dias. Os cães foram avaliados em quatro momentos (T0, T14, T28 e T56 dias) quanto aos sinais clínicos e parâmetros hematológicos e bioquímico-séricos, que incluíram concentrações séricas da enzima conversora da angiotensina (ECA) e aldosterona, como também avaliações radiográficas, eletrocardiográficas, ecodopplercardiográficas e da pressão arterial. Os resultados quanto aos parâmetros clínicos, avaliações hematológicas e bioquímicas séricas não revelaram alterações significativas em ambos os grupos, mas reduções significativas nos valores de ECA e aldosterona no grupo que recebeu o maleato de enalapril foram identificadas. Ao exame radiográfico observou-se reduções nos valores de VHS e na variável onda Pms do eletrocardiograma em ambos os grupos, mas sem alterações nos valores da pressão arterial. Por sua vez, o ecodopplercardiograma evidenciou diminuição significativa das variáveis DIVEd/s nos grupos estudados e na FEC% nos cães que receberam somente enalapril. Portanto, a análise dos resultados encontrados indicou que a monoterapia fundamentada no maleato de enalapril apresentou melhor eficiência no controle do quadro clínico em pacientes da classe funcional Ib da ICC.

Bacterial functional redundancy along a soil reclamation gradient

A strategy to measure bacterial functional redundancy was developed and tested with soils collected along a soil reclamation gradient by determining the richness and diversity of bacterial groups capable of in situ growth on selected carbon substrates. Soil cores were collected from four sites along a transect from the Jamari tin mine site in the Jamari National Forest, Rondonia, RO, Brazil: denuded mine spoil, soil from below the canopy of invading pioneer trees, revegetated soil under new growth on the forest edge, and the forest floor of an adjacent preserved forest. Bacterial population responses were analyzed by amending these soil samples with individual carbon substrates in the presence of bromodeoxyuridine (BrdU), BrdU-labeled DNA was then subjected to a 16S-23S rRNA intergenic analysis to depict the actively growing bacteria from each site, the number and diversity of bacterial groups responding to four carbon substrates (L-serine, L-threonine, sodium citrate, and or-lactose hydrate) increased along the reclamation-vegetation gradient such that the preserved forest soil samples contained the highest functional redundancy for each substrate. These data suggest that bacterial functional redundancy increases in relation to the regrowth of plant communities and may therefore represent an important aspect of the restoration of soil biological functionality to reclaimed mine spoils. They also suggest that bacterial functional redundancy may be a useful indicator of soil quality and ecosystem functioning.

Nest Digging by Leaf-Cutting Ants: Effect of Group Size and Functional Structures.

Leaf-cutting ant workers dig underground chambers, for housing their symbiotic fungus, interconnected by a vast quantity of tunnels whose function is to permit the entrance of food (leaves), gaseous exchanges, andmovement of workers, offspring, and the queen. Digging is a task executed by a group of workers, but little is known about the group effect and group-constructed functional structures. Thus, we analyzed the structures formed by worker groups (5, 10, 20, and 40 individuals) of the leaf-cutting ant, Atta sexdens rubropilosa, for 2 days of excavation. The digging arena was the same for the 4 groups, with each group corresponding to a different density. Our results verified a pattern of tunneling by the workers, but no chamber was constructed. The group effect is well known, since the 40-worker group dug significantly more than the groups of 5, 10, and 20. These groups did not differ statistically from each other. Analysis of load/worker verified that workers of the smallest group carried the greatest load. Our paper demonstrates the group effect on the digging of nests, namely, that excavation is proportional to group size, but without emergence of a functional structure such as a chamber.

Ecological distribution of stream macroalgae in different spatial scales using taxonomic and morphological groups

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Postural control and functional balance in individuals with diabetic peripheral neuropathy

A Neuropatia diabética periférica (NDP) cursa com redução somatossensitiva que pode levar a alterações no controle postural. O objetivo do estudo foi avaliar o controle postural na postura ereta, em diferentes condições, e o equilíbrio funcional em indivíduos com NDP, correlacionar os resultados obtidos na avaliação do controle postural com os valores do teste do equilíbrio funcional e comparar os resultados obtidos no grupo neuropata com o grupo controle, verificando as possíveis diferenças entre as condições de avaliação em ambos os grupos. Participaram do estudo 13 mulheres com NDP (GN) e 17 mulheres não diabéticas (GC). A avaliação do controle postural foi realizada por cinemetria nas condições: olhos abertos (OA), olhos fechados (OF) e semi tandem (ST). Após processamento no MATLAB, foram geradas as variáveis: amplitude média de oscilação (AMO) na direção ântero-posterior (AP) e médio-lateral (ML); e velocidade média de oscilação (VMO) na direção AP e ML. O equilíbrio funcional foi avaliado pelo Timed Up and Go Test. Houve diferença significante entre os grupos (p<0,005) na AMO-AP OA e OF, AMO-ML of e ST e VMO-ML ST. Houve diferença entre as condições OA e ST (p<0,005) e of e ST (p<0,005) para as variáveis AMO-ML e VMO-ML, com maior prejuízo para o GN, que também apresentou um menor equilíbrio funcional (p=0,001). A instabilidade ML foi correlacionada positivamente com o desequilíbrio funcional. Os resultados nos mostram uma alteração no sistema de controle postural na NDP, o que pode levar estes indivíduos a um maior risco a quedas e prejuízos funcionais.

Influence of respiratory biofeedback associated to re-expansive ventilation patterns in individuals with functional mouth breathing

Objectives: Assess the effect of re-expansive respiratory patterns associated to respiratory biofeedback (RBF) on pulmonary function, respiratory muscle strength and habits in individuals with functional mouth breathing (FMB).Methods: Sixty children with FMB were divided into experimental and control groups. The experimental group was submitted to 15 sessions of re-expansive respiratory patterns associated to RBF (biofeedback pletsmovent; MICROHARD (R) V1.0), which provided biofeedback of the thoracic and abdominal movements. The control group was submitted to 15 sessions using biofeedback alone. Spirometry, maximum static respiratory pressure measurements and questions regarding habits (answered by parents/guardians) were carried out before and after therapy. The Student's t-test for paired data and non-parametric tests were employed for statistical analysis at a 5% Level of significance.Results: Significant changes were found in forced vital. capacity, Tiffeneau index scores, maximum expiratory pressure, maximum inspiratory pressure and habits assessed in FMB with the use of RBF associated to the re-expansive patterns. No significant differences were found comparing the experimental and control groups.Conclusions: The results allow the conclusion that RBF associated to re-expansive patterns improves forced vital capacity, Tiffeneau index scores, respiratory muscle strength and habits in FMB and can therefore be used as a form of therapy for such individuals. (C) 2008 Elsevier B.V. All rights reserved.

Functional alterations in endocrine pancreas of rats with different degrees of dexamethasone-induced insulin resistance

Objectives: We have analyzed the peripheral insulin and glucose sensitivity in vivo, and islet function ex vivo in rats with different degrees of insulin resistance induced by dexamethasone (DEX).Methods: Dexamethasone, in the concentrations of 0.1 (DEX 0.1), 0.5 (DEX 0.5), and 1.0 mg/kg body weight (DEX 1.0) was administered daily, intraperitoneally, to adult Wistar rats for 5 days, whereas controls received saline.Results: Dexamethasone treatment induced peripheral insulin resistance in a dose-dependent manner. At the end of the treatment, only DEX 1.0 rats showed significant increase of postabsorptive blood glucose and serum triglycerides, and nonesterified fatty acids levels. Incubation of pancreatic islets in increasing glucose concentrations (2.8-22 mM) led to an augmented insulin secretion in all DEX-treated rats. Leucine, carbachol, and high KCl concentrations induced the insulin release in DEX 0.5 and DEX 1.0, whereas arginine augmented secretion in all DEX-treated groups.Conclusions: We demonstrate that in DEX 0.5 and, especially in DEX 0.1 groups, but not in DEX 1.0, the adaptations that occurred in the endocrine pancreas are able to counteract metabolic disorders (glucose intolerance and dyslipidemia). These animal models seem to be interesting approaches for the study of degrees of subjacent effects that may mediate type 2 diabetes (DEX 1.0) and islet function alterations, without collateral effects (DEX 0.1 and DEX 0.5).