The effect of clozapine on mRNA expression for genes encoding G protein-coupled receptors and the protein components of clathrin-mediated endocytosis.

Clathrin-mediated endocytosis (CME) is an intracellular trafficking mechanism for packaging cargo, including G protein-coupled receptors (GPCRs), into clathrin-coated vesicles (CCVs). The antipsychotic chlorpromazine inhibits CCV assembly of adaptor protein AP2 whereas clozapine increases serotonin2A receptor internalization. We hypothesized that clozapine alters the expression of CME genes modulating vesicle turnover and GPCR internalization

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Clinicopathological Profile and Surgical Treatment of Abdominal Tuberculosis: A Single Centre Experience in Northwestern Tanzania.

Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16-68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival

Photosynthesis by six portuguese maize cultivars during drought stress and recovery

Photosynthesis, chlorophyll fluorescence and leaf water parameters were measured in six Portuguese maize (Zea mays L.) cultivars during and following a period of drought stress. The leaf relative water content (RWC) responded differently among cultivars but, except for cultivar PB369, recovered close to initial values after watering was restored. Photosynthetic rate and stomatal conductance decreased with drought but more slowly in cultivars PB269 and PB260 than in cultivars AD3R, PB64, PB304 and PB369. Water use efficiency (WUE) decreased during the water stress treatment although with cultivar PB260 the decrease was marked only when the RWC fell below 40%. Recovery of WUE was seen with all cultivars except PB369. The maximum quantum efficiency of photosystem II, the photochemical quenching coefficient, the electron transport rate in PSII and the estimated functional plastoquinone pool tended to decrease with drought, while the non -photochemical quenching coefficient increased. The parameters estimated from chlorophyll fluorescence did not recover in PB369, during re - watering. The results show that PB260 and PB269 were the most tolerant and PB369 was the least tolerant cultivars to water stress. The variation found amongst the cultivars tested suggests the existence of valuable genetic resources for crop improvement in relation to drought tolerance

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas

Galaxy And Mass Assembly (GAMA): the effect of close interactions on star formation in galaxies

The modification of star formation (SF) in galaxy interactions is a complex process, with SF observed to be both enhanced in major mergers and suppressed in minor pair interactions. Such changes likely to arise on short timescales and be directly related to the galaxy-galaxy interaction time. Here we investigate the link between dynamical phase and direct measures of SF on different timescales for pair galaxies, targeting numerous star-formation rate (SFR) indicators and comparing to pair separation, individual galaxy mass and pair mass ratio. We split our sample into the higher (primary) and lower (secondary) mass galaxies in each pair and find that SF is indeed enhanced in all primary galaxies but suppressed in secondaries of minor mergers. We find that changes in SF of primaries is consistent in both major and minor mergers, suggesting that SF in the more massive galaxy is agnostic to pair mass ratio. We also find that SF is enhanced/suppressed more strongly for short-time duration SFR indicators (e.g. H-alpha), highlighting recent changes to SF in these galaxies, which are likely to be induced by the interaction. We propose a scenario where the lower mass galaxy has its SF suppressed by gas heating or stripping, while the higher mass galaxy has its SF enhanced, potentially by tidal gas turbulence and shocks. This is consistent with the seemingly contradictory observations for both SF suppression and enhancement in close pairs

Galaxy And Mass Assembly (GAMA): the effect of close interactions on star formation in galaxies

The modification of star formation (SF) in galaxy interactions is a complex process, with SF observed to be both enhanced in major mergers and suppressed in minor pair interactions. Such changes likely to arise on short timescales and be directly related to the galaxy-galaxy interaction time. Here we investigate the link between dynamical phase and direct measures of SF on different timescales for pair galaxies, targeting numerous star-formation rate (SFR) indicators and comparing to pair separation, individual galaxy mass and pair mass ratio. We split our sample into the higher (primary) and lower (secondary) mass galaxies in each pair and find that SF is indeed enhanced in all primary galaxies but suppressed in secondaries of minor mergers. We find that changes in SF of primaries is consistent in both major and minor mergers, suggesting that SF in the more massive galaxy is agnostic to pair mass ratio. We also find that SF is enhanced/suppressed more strongly for short-time duration SFR indicators (e.g. H-alpha), highlighting recent changes to SF in these galaxies, which are likely to be induced by the interaction. We propose a scenario where the lower mass galaxy has its SF suppressed by gas heating or stripping, while the higher mass galaxy has its SF enhanced, potentially by tidal gas turbulence and shocks. This is consistent with the seemingly contradictory observations for both SF suppression and enhancement in close pairs

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Item response theory analysis of the recoded Internet Gaming Disorder Scale-Short-Form (IGDS9-SF)

Based on the nine criteria for Internet gaming disorder (IGD) in DSM-5, the Internet Gaming Disorder Scale 9-Short Form (IGDS9-SF; Pontes and Griffiths 2015) is the most widely used questionnaire for assessing IGD. The present study examined support for the unidimensional factor structure of the instrument, with a group of 868 adolescent and adult gamers from the USA, with criteria recoded as present or absent. The two-parameter logistic model (2PLM) was used to examine the item response theory properties of the criteria included in the measure. Confirmatory factor analysis supported the one-factor model. The 2PLM analysis indicated that all the criteria were strong discriminators of high and low latent IGD. Furthermore, the items measured more of the GAD dimension and with more precision from around +2 SD from the mean trait level. The implications of the findings for interpreting the IGDS9-SF scores for clinical practice are discussed

Interpretation and expectation in childhood anxiety disorders: age effects and social specificity

Theory and treatment for childhood anxiety disorders typically implicates children’s negative cognitions, yet little is known about the characteristics of thinking styles of clinically anxious children. In particular, it is unclear whether differences in thinking styles between children with anxiety disorders and non-anxious children vary as a function of child age, whether particular cognitive distortions are associated with childhood anxiety disorders at different child ages, and whether cognitive content is disorder-specific. The current study addressed these questions among 120 7 - 12 year old children (53% female) who met diagnostic criteria for social anxiety disorder, other anxiety disorder, or who were not currently anxious. Contrary to expectations, threat interpretation was not inflated amongst anxious compared to non-anxious children at any age, although older (10 - 12 year old) anxious children did differ from non-anxious children on measures of perceived coping. The notion of cognitive-content specificity was not supported across the age-range. The findings challenge current treatment models of childhood anxiety, and suggest that a focus on changing anxious children’s cognitions is not warranted in mid-childhood, and in late childhood cognitive approaches may be better focussed on promoting children’s perceptions of control rather than challenging threat interpretations