A systematic experimental neuropsychological investigation of the functional integrity of working memory circuits in major depression

Verbal and visuospatial working memory (WM) impairment is a well-documented finding in psychiatric patients suffering from major psychoses such as schizophrenia or bipolar affective disorder. However, in major depression (MDD) the literature on the presence and the extent of WM deficits is inconsistent. The use of a multitude of different WM tasks most of which lack process-specificity may have contributed to these inconsistencies. Eighteen MDD patients and 18 healthy controls matched with regard to age, gender and education were tested using process- and circuit-specific WM tasks for which clear brain-behaviour relationships had been established in prior functional neuroimaging studies. Patients suffering from acute MDD showed a selective impairment in articulatory rehearsal of verbal information in working memory. By contrast, visuospatial WM was unimpaired in this sample. There were no significant correlations between symptom severity and WM performance. These data indicate a dysfunction of a specific verbal WM system in acutely ill patients with MDD. As the observed functional deficit did not correlate with different symptom scores, further, longitudinal studies are required to clarify whether and how this deficit is related to illness acuity and clinical state of MDD patients

Answering biological questions: querying a systems biology database for nutrigenomics

The requirement of systems biology for connecting different levels of biological research leads directly to a need for integrating vast amounts of diverse information in general and of omics data in particular. The nutritional phenotype database addresses this challenge for nutrigenomics. A particularly urgent objective in coping with the data avalanche is making biologically meaningful information accessible to the researcher. This contribution describes how we intend to meet this objective with the nutritional phenotype database. We outline relevant parts of the system architecture, describe the kinds of data managed by it, and show how the system can support retrieval of biologically meaningful information by means of ontologies, full-text queries, and structured queries. Our contribution points out critical points, describes several technical hurdles. It demonstrates how pathway analysis can improve queries and comparisons for nutrition studies. Finally, three directions for future research are given

Real-time pH monitoring of industrially relevant enzymatic reactions in a microfluidic side-entry reactor (μSER) shows potential for pH control

Monitoring and control of pH is essential for the control of reaction conditions and reaction progress for any biocatalytic or biotechnological process. Microfluidic enzymatic reactors are increasingly proposed for process development, however typically lack instrumentation, such as pH monitoring. We present a microfluidic side-entry reactor (μSER) and demonstrate for the first time real-time pH monitoring of the progression of an enzymatic reaction in a microfluidic reactor as a first step towards achieving pH control. Two different types of optical pH sensors were integrated at several positions in the reactor channel which enabled pH monitoring between pH 3.5 and pH 8.5, thus a broader range than typically reported. The sensors withstood the thermal bonding temperatures typical of microfluidic device fabrication. Additionally, fluidic inputs along the reaction channel were implemented to adjust the pH of the reaction. Time-course profiles of pH were recorded for a transketolase and a penicillin G acylase catalyzed reaction. Without pH adjustment, the former showed a pH increase of 1 pH unit and the latter a pH decrease of about 2.5 pH units. With pH adjustment, the pH drop of the penicillin G acylase catalyzed reaction was significantly attenuated, the reaction condition kept at a pH suitable for the operation of the enzyme, and the product yield increased. This contribution represents a further step towards fully instrumented and controlled microfluidic reactors for biocatalytic process development

Atherosclerosis of the descending aorta predicts cardiovascular events: a transesophageal echocardiography study

PURPOSE: Previous studies have shown that atherosclerosis of the descending aorta detected by transesophageal echocardiography (TEE) is a good marker of coexisting coronary artery disease. The aim of our study was to evaluate whether the presence of atherosclerosis on the descending aorta during TEE has any prognostic impact in predicting cardiovascular events. MATERIAL AND METHODS: The study group consisted of 238 consecutive in-hospital patients referred for TEE testing (135 males, 103 females, mean age 58 +/- 11 years) with a follow up of 24 months. The atherosclerotic lesions of the descending aorta were scored from 0 (no atherosclerosis) to 3 (plaque >5 mm and/or "complex" plaque with ulcerated or mobile parts). RESULTS: Atherosclerosis was observed in 102 patients, (grade 3 in 16, and grade 2 in 86 patients) whereas 136 patients only had an intimal thickening or normal intimal surface. There were 57 cardiovascular events in the follow-up period. The number of events was higher in the 102 patients with (n = 34) than in the 136 patients without atherosclerosis (n = 23, p < 0.01). The frequency of events was in close correlation with the severity of the atherosclerosis of the descending aorta. Fifty percent of the patients with grade 3 experienced cardiovascular events. Excluding patients with subsequent revascularization, the multivariate analysis only left ventricular function with EF < 40% (HR 3.0, CI 1.3–7.1) and TEE atherosclerotic plaque >=2 (HR 2.4, CI 1.0–5.5) predicted hard cardiovascular events. CONCLUSION: Atherosclerosis of the descending aorta observed during transesophageal echocardiography is a useful predictor of cardiovascular events

Smoking reduces surfactant protein D and phospholipids in patients with and without chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>Pulmonary surfactant D (SP-D) has important regulatory functions for innate immunity and has been implicated as a biomarker for chronic obstructive pulmonary disease (COPD). We hypothesized that COPD patients would have reduced bronchoalveolar lavage (BAL) fluid SP-D levels compared to healthy smoking and non-smoking controls.</p> <p>Methods</p> <p>BAL SP-D and phospholipids were quantified and corrected for dilution in 110 subjects (65 healthy never smokers, 23 smokers with normal spirometry, and 22 smokers with COPD).</p> <p>Results</p> <p>BAL SP-D was highest in never smokers (mean 51.9 μg/mL ± 7.1 μg/mL standard error) compared to both smokers with normal spirometry (16.0 μg/mL ± 11.8 μg/mL) and subjects with COPD (19.1 μg/mL ± 12.9 μg/mL; P < 0.0001). Among smokers with COPD, BAL SP-D correlated significantly with FEV₁% predicted (R = 0.43; P < 0.05); however, the strongest predictor of BAL SP-D was smoking status. BAL SP-D levels were lowest in current smokers (12.8 μg/mL ± 11.0 μg/mL), intermediate in former smokers (25.2 μg/mL ± 14.2 μg/mL; P < 0.008), and highest in never smokers. BAL phospholipids were also lowest in current smokers (6.5 nmol ± 1.5 nmol), intermediate in former smokers (13.1 nmol ± 2.1 nmol), and highest in never smokers (14.8 nmol ± 1.1 nmol; P < 0.0001).</p> <p>Conclusions</p> <p>These data suggest that smokers, and especially current smokers, exhibit significantly reduced BAL SP-D and phospholipids compared to nonsmokers. Our findings may help better explain the mechanism that leads to the rapid progression of disease and increased incidence of infection in smokers.</p

Early respiratory morbidity in a multicultural birth cohort: the Generation R Study

Ethnic disparities in the prevalence of asthma symptoms in children have been described. We evaluated to what extent the association between ethnic background and respiratory symptoms during the first 2 years of life could be explained by the mediating effect of risk factors for respiratory morbidity. The Generation R Study is a multiethnic, population-based birth cohort study. Pre and postnatal risk factors for respiratory morbidity were prospectively assessed by questionnaires. Information about ethnicity was available for 5,684 infants. The associations between ethnic background and lower respiratory symptoms at 12 and 24 months were evaluated with log-binomial regression models. Relative risks and 95 % confidence intervals (RR [95 % CI]) were computed for Cape Verdean, Moroccan, Antillean, Surinamese and Turkish ethnicity with Dutch ethnicity as the reference category. We found an increased risk of lower respiratory symptoms at 24 months in Antillean infants (1.32 [95 % CI 1.12–1.57]) that was mediated by early postnatal exposures (pets keeping, siblings, breastfeeding, daycare attendance, smoke exposure). Turkish infants also had an increased risk of lower respiratory symptoms at 12 and 24 months (1.14 [95 % CI 1.02–1.27] and 1.21 [95 % CI 1.07–1.38], respectively), partly explained by previous morbidity (eczema, infections and upper respiratory symptoms). There were no differences for Cape Verdean, Moroccan or Surinamese, as compared to Dutch infants. Hence, ethnic background was associated with respiratory symptoms during the first 2 years of life and this association was largely explained by mediating effects of known pre and postnatal risk factors for respiratory morbidity

Prediction of Depression in Individuals at High Familial Risk of Mood Disorders Using Functional Magnetic Resonance Imaging

Objective Bipolar disorder is a highly heritable condition. First-degree relatives of affected individuals have a more than a ten-fold increased risk of developing bipolar disorder (BD), and a three-fold risk of developing major depressive disorder (MDD) than the general population. It is unclear however whether differences in brain activation reported in BD and MDD are present before the onset of illness. Methods We studied 98 young unaffected individuals at high familial risk of BD and 58 healthy controls using functional Magnetic Resonance Imaging (fMRI) scans and a task involving executive and language processing. Twenty of the high-risk subjects subsequently developed MDD after the baseline fMRI scan. Results At baseline the high-risk subjects who later developed MDD demonstrated relatively increased activation in the insula cortex, compared to controls and high risk subjects who remained well. In the healthy controls and high-risk group who remained well, this region demonstrated reduced engagement with increasing task difficulty. The high risk subjects who subsequently developed MDD did not demonstrate this normal disengagement. Activation in this region correlated positively with measures of cyclothymia and neuroticism at baseline, but not with measures of depression. Conclusions These results suggest that increased activation of the insula can differentiate individuals at high-risk of bipolar disorder who later develop MDD from healthy controls and those at familial risk who remain well. These findings offer the potential of future risk stratification in individuals at risk of mood disorder for familial reasons

Online dispute resolution: an artificial intelligence perspective

Litigation in court is still the main dispute resolution mode. However, given the amount and characteristics of the new disputes, mostly arising out of electronic contracting, courts are becoming slower and outdated. Online Dispute Resolution (ODR) recently emerged as a set of tools and techniques, supported by technology, aimed at facilitating conflict resolution. In this paper we present a critical evaluation on the use of Artificial Intelligence (AI) based techniques in ODR. In order to fulfill this goal, we analyze a set of commercial providers (in this case twenty four) and some research projects (in this circumstance six). Supported by the results so far achieved, a new approach to deal with the problem of ODR is proposed, in which we take on some of the problems identified in the current state of the art in linking ODR and AI.The work described in this paper is included in TIARAC - Telematics and Artificial Intelligence in Alternative Conflict Resolution Project (PTDC/JUR/71354/2006), which is a research project supported by FCT (Science & Technology Foundation), Portugal. The work of Davide Carneiro is also supported by a doctoral grant by FCT (SFRH/BD/64890/2009).Acknowledgments. The work described in this paper is included in TIARAC - Telematics and Artificial Intelligence in Alternative Conflict Resolution Project (PTDC/JUR/71354/2006), which is a research project supported by FCT (Science & Technology Foundation), Portugal. The work of Davide Carneiro is also supported by a doctoral grant by FCT (SFRH/BD/64890/2009)

A Gene in the Process of Endosymbiotic Transfer

BACKGROUND: The endosymbiotic birth of organelles is accompanied by massive transfer of endosymbiont genes to the eukaryotic host nucleus. In the centric diatom Thalassiosira pseudonana the Psb28 protein is encoded in the plastid genome while a second version is nuclear-encoded and possesses a bipartite N-terminal presequence necessary to target the protein into the diatom complex plastid. Thus it can represent a gene captured during endosymbiotic gene transfer. METHODOLOGY/PRINCIPAL FINDINGS: To specify the origin of nuclear- and plastid-encoded Psb28 in T. pseudonana we have performed extensive phylogenetic analyses of both mentioned genes. We have also experimentally tested the intracellular location of the nuclear-encoded Psb28 protein (nuPsb28) through transformation of the diatom Phaeodactylum tricornutum with the gene in question fused to EYFP. CONCLUSIONS/SIGNIFICANCE: We show here that both versions of the psb28 gene in T. pseudonana are transcribed. We also provide experimental evidence for successful targeting of the nuPsb28 fused with EYFP to the diatom complex plastid. Extensive phylogenetic analyses demonstrate that nucleotide composition of the analyzed genes deeply influences the tree topology and that appropriate methods designed to deal with a compositional bias of the sequences and the long branch attraction artefact (LBA) need to be used to overcome this obstacle. We propose that nuclear psb28 in T. pseudonana is a duplicate of a plastid localized version, and that it has been transferred from its endosymbiont

The comparative osmoregulatory ability of two water beetle genera whose species span the fresh-hypersaline gradient in inland waters (Coleoptera: Dytiscidae, Hydrophilidae).

A better knowledge of the physiological basis of salinity tolerance is essential to understanding the ecology and evolutionary history of organisms that have colonized inland saline waters. Coleoptera are amongst the most diverse macroinvertebrates in inland waters, including saline habitats; however, the osmoregulatory strategies they employ to deal with osmotic stress remain unexplored. Survival and haemolymph osmotic concentration at different salinities were examined in adults of eight aquatic beetle species which inhabit different parts of the fresh-hypersaline gradient. Studied species belong to two unrelated genera which have invaded saline waters independently from freshwater ancestors; Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae). Their osmoregulatory strategy (osmoconformity or osmoregulation) was identified and osmotic capacity (the osmotic gradient between the animal's haemolymph and the external medium) was compared between species pairs co-habiting similar salinities in nature. We show that osmoregulatory capacity, rather than osmoconformity, has evolved independently in these different lineages. All species hyperegulated their haemolymph osmotic concentration in diluted waters; those living in fresh or low-salinity waters were unable to hyporegulate and survive in hyperosmotic media (> 340 mosmol kg(-1)). In contrast, the species which inhabit the hypo-hypersaline habitats were effective hyporegulators, maintaining their haemolymph osmolality within narrow limits (ca. 300 mosmol kg(-1)) across a wide range of external concentrations. The hypersaline species N. ceresyi and E. jesusarribasi tolerated conductivities up to 140 and 180 mS cm(-1), respectively, and maintained osmotic gradients over 3500 mosmol kg(-1), comparable to those of the most effective insect osmoregulators known to date. Syntopic species of both genera showed similar osmotic capacities and in general, osmotic responses correlated well with upper salinity levels occupied by individual species in nature. Therefore, osmoregulatory capacity may mediate habitat segregation amongst congeners across the salinity gradient