The antisaccade task as an index of sustained goal activation in working memory: modulation by nicotine

The antisaccade task provides a laboratory analogue of situations in which execution of the correct behavioural response requires the suppression of a more prepotent or habitual response. Errors (failures to inhibit a reflexive prosaccade towards a sudden onset target) are significantly increased in patients with damage to the dorsolateral prefrontal cortex and patients with schizophrenia. Recent models of antisaccade performance suggest that errors are more likely to occur when the intention to initiate an antisaccade is insufficiently activated within working memory. Nicotine has been shown to enhance specific working memory processes in healthy adults. MATERIALS AND METHODS: We explored the effect of nicotine on antisaccade performance in a large sample (N = 44) of young adult smokers. Minimally abstinent participants attended two test sessions and were asked to smoke one of their own cigarettes between baseline and retest during one session only. RESULTS AND CONCLUSION: Nicotine reduced antisaccade errors and correct antisaccade latencies if delivered before optimum performance levels are achieved, suggesting that nicotine supports the activation of intentions in working memory during task performance. The implications of this research for current theoretical accounts of antisaccade performance, and for interpreting the increased rate of antisaccade errors found in some psychiatric patient groups are discussed

Differences in Disease Severity but Similar Telomere Lengths in Genetic Subgroups of Patients with Telomerase and Shelterin Mutations

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Homocysteine, Grey Matter and Cognitive Function in Adults with Cardiovascular Disease

Background: Elevated total plasma homocysteine (tHcy) has been associated with cognitive impairment, vascular disease and brain atrophy. Methods: We investigated 150 volunteers to determine if the association between high tHcy and cerebral grey matter volume and cognitive function is independent of cardiovascular disease. Results: Participants with high tHcy ($15 mmol/L) showed a widespread relative loss of grey matter compared with people with normal tHcy, although differences between the groups were minimal once the analyses were adjusted for age, gender, diabetes, hypertension, smoking and prevalent cardiovascular disease. Individuals with high tHcy had worse cognitive scores across a range of domains and less total grey matter volume, although these differences were not significant in the adjusted models. Conclusions: Our results suggest that the association between high tHcy and loss of cerebral grey matter volume and decline in cognitive function is largely explained by increasing age and cardiovascular diseases and indicate that th

Structures of the Signal Recognition Particle Receptor from the Archaeon Pyrococcus furiosus: Implications for the Targeting Step at the Membrane

In all organisms, a ribonucleoprotein called the signal recognition particle (SRP) and its receptor (SR) target nascent proteins from the ribosome to the translocon for secretion or membrane insertion. We present the first X-ray structures of an archeal FtsY, the receptor from the hyper-thermophile Pyrococcus furiosus (Pfu), in its free and GDP•magnesium-bound forms. The highly charged N-terminal domain of Pfu-FtsY is distinguished by a long N-terminal helix. The basic charges on the surface of this helix are likely to regulate interactions at the membrane. A peripheral GDP bound near a regulatory motif could indicate a site of interaction between the receptor and ribosomal or SRP RNAs. Small angle X-ray scattering and analytical ultracentrifugation indicate that the crystal structure of Pfu-FtsY correlates well with the average conformation in solution. Based on previous structures of two sub-complexes, we propose a model of the core of archeal and eukaryotic SRP•SR targeting complexes

Binge eating, purging and non-purging compensatory behaviours decrease from adolescence to adulthood: A population-based, longitudinal study

Background Subclinical forms of eating disorders (ED) are highly prevalent, but relatively little is known about age trends, gender differences and distinctions among symptoms. This study investigates age trends and gender difference in binge eating, purging and non-purging compensatory behaviours (CB) and the relationship of such behaviours to psychosocial problems. Methods Data from the national representative longitudinal study "Young in Norway" (ages 14-34 years) were analysed using χ 2 tests, logistic random intercept models and analyses of covariance. Results For both genders, a decrease was found in the prevalence of CB from age 14-16 years to 23 years and over. For binging, however, a significant decrease was found only for females, whose binge eating also declined more markedly over time than did males'. A significant gender difference was detected for purging, with females at higher risk. Purging was related to particularly serious symptoms of psychosocial problems: Those who purged had significantly higher levels of appearance dissatisfaction, anxiety and depressive symptoms, alcohol consumption, self-concept instability and loneliness than those with symptoms of other forms of disordered eating. Conclusions Individuals affected by purging need to be targeted as a high-risk group. The distinction in severity among the subclinical ED may indicate the need for the reformulation of the eating disorder not otherwise specified category in the Diagnostic and Statistical Manual of Mental Disorders-V

Diagnosis of invasive candidiasis in the ICU

Invasive candidiasis ranges from 5 to 10 cases per 1,000 ICU admissions and represents 5% to 10% of all ICU-acquired infections, with an overall mortality comparable to that of severe sepsis/septic shock. A large majority of them are due to Candida albicans, but the proportion of strains with decreased sensitivity or resistance to fluconazole is increasingly reported. A high proportion of ICU patients become colonized, but only 5% to 30% of them develop an invasive infection. Progressive colonization and major abdominal surgery are common risk factors, but invasive candidiasis is difficult to predict and early diagnosis remains a major challenge. Indeed, blood cultures are positive in a minority of cases and often late in the course of infection. New nonculture-based laboratory techniques may contribute to early diagnosis and management of invasive candidiasis. Both serologic (mannan, antimannan, and betaglucan) and molecular (Candida-specific PCR in blood and serum) have been applied as serial screening procedures in high-risk patients. However, although reasonably sensitive and specific, these techniques are largely investigational and their clinical usefulness remains to be established. Identification of patients susceptible to benefit from empirical antifungal treatment remains challenging, but it is mandatory to avoid antifungal overuse in critically ill patients. Growing evidence suggests that monitoring the dynamic of Candida colonization in surgical patients and prediction rules based on combined risk factors may be used to identify ICU patients at high risk of invasive candidiasis susceptible to benefit from prophylaxis or preemptive antifungal treatment

How DNA Barcodes Complement Taxonomy and Explore Species Diversity: The Case Study of a Poorly Understood Marine Fauna

BACKGROUND: The species boundaries of some venerids are difficult to define based solely on morphological features due to their indistinct intra- and interspecific phenotypic variability. An unprecedented biodiversity crisis caused by human activities has emerged. Thus, to access the biological diversity and further the conservation of this taxonomically muddling bivalve group, a fast and simple approach that can efficiently examine species boundaries and highlight areas of unrecognized diversity is urgently needed. DNA barcoding has proved its effectiveness in high-volume species identification and discovery. In the present study, Chinese fauna was chosen to examine whether this molecular biomarker is sensitive enough for species delimitation, and how it complements taxonomy and explores species diversity. METHODOLOGY/PRINCIPAL FINDINGS: A total of 315 specimens from around 60 venerid species were included, qualifying the present study as the first major analysis of DNA barcoding for marine bivalves. Nearly all individuals identified to species level based on morphological traits possessed distinct barcode clusters, except for the specimens of one species pair. Among the 26 individuals that were not assigned binomial names a priori, twelve respectively nested within a species genealogy. The remaining individuals formed five monophyletic clusters that potentially represent species new to science or at least unreported in China. Five putative hidden species were also uncovered in traditional morphospecies. CONCLUSIONS/SIGNIFICANCE: The present study shows that DNA barcoding is effective in species delimitation and can aid taxonomists by indicating useful diagnostic morphological traits, informing needful revision, and flagging unseen species. Moreover, the BOLD system, which deposits barcodes, morphological, geographical and other data, has the potential as a convenient taxonomic platform

Direct Visualization of Peptide/MHC Complexes at the Surface and in the Intracellular Compartments of Cells Infected In Vivo by Leishmania major

Protozoa and bacteria infect various types of phagocytic cells including macrophages, monocytes, dendritic cells and eosinophils. However, it is not clear which of these cells process and present microbial antigens in vivo and in which cellular compartments parasite peptides are loaded onto Major Histocompatibility Complex molecules. To address these issues, we have infected susceptible BALB/c (H-2d) mice with a recombinant Leishmania major parasite expressing a fluorescent tracer. To directly visualize the antigen presenting cells that present parasite-derived peptides to CD4+ T cells, we have generated a monoclonal antibody that reacts to an antigenic peptide derived from the parasite LACK antigen bound to I-Ad Major Histocompatibility Complex class II molecule. Immunogold electron microscopic analysis of in vivo infected cells showed that intracellular I-Ad/LACK complexes were present in the membrane of amastigote-containing phagosomes in dendritic cells, eosinophils and macrophages/monocytes. In both dendritic cells and macrophages, these complexes were also present in smaller vesicles that did not contain amastigote. The presence of I-Ad/LACK complexes at the surface of dendritic cells, but neither on the plasma membrane of macrophages nor eosinophils was independently confirmed by flow cytometry and by incubating sorted phagocytes with highly sensitive LACK-specific hybridomas. Altogether, our results suggest that peptides derived from Leishmania proteins are loaded onto Major Histocompatibility Complex class II molecules in the phagosomes of infected phagocytes. Although these complexes are transported to the cell surface in dendritic cells, therefore allowing the stimulation of parasite-specific CD4+ T cells, this does not occur in other phagocytic cells. To our knowledge, this is the first study in which Major Histocompatibility Complex class II molecules bound to peptides derived from a parasite protein have been visualized within and at the surface of cells that were infected in vivo

A sub-Neptune transiting the young field star HD 18599 at 40 pc

Transiting exoplanets orbiting young nearby stars are ideal laboratories for testing theories of planet formation and evolution. However, to date only a handful of stars with age <1 Gyr have been found to host transiting exoplanets. Here we present the discovery and validation of a sub-Neptune around HD 18599 , a young (300 Myr), nearby (d = 40 pc) K star. We validate the transiting planet candidate as a bona fide planet using data from the TESS , Spitzer , and Gaia  missions, ground-based photometry from IRSF , LCO , PEST , and NGTS , speckle imaging from Gemini, and spectroscopy from CHIRON , NRES , FEROS , and Minerva-Australis . The planet has an orbital period of 4.13 d , and a radius of 2.7 R⊕ . The RV data yields a 3-σ mass upper limit of 30.5 M⊕  which is explained by either a massive companion or the large observed jitter typical for a young star. The brightness of the host star (V∼9 mag) makes it conducive to detailed characterization via Doppler mass measurement which will provide a rare view into the interior structure of young planets

Genetic risk profiles for depression and anxiety in adult and elderly cohorts

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ∼0.7% of the variance in depression in Rotterdam Study and up to ∼1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples