Chewing-gum flavor affects measures of global complexity of multichannel EEG

Global complexity of spontaneous brain electric activity was studied before and after chewing gum without flavor and with 2 different flavors. One-minute, 19-channel, eyes-closed electroencephalograms (EEG) were recorded from 20 healthy males before and after using 3 types of chewing gum: regular gum containing sugar and aromatic additives, gum containing 200 mg theanine (a constituent of Japanese green tea), and gum base (no sugar, no aromatic additives); each was chewed for 5 min in randomized sequence. Brain electric activity was assessed through Global Omega (Ω)-Complexity and Global Dimensional Complexity (GDC), quantitative measures of complexity of the trajectory of EEG map series in state space; their differences from pre-chewing data were compared across gum-chewing conditions. Friedman Anova (p < 0.043) showed that effects on Ω-Complexity differed significantly between conditions and differences were maximal between gum base and theanine gum. No differences were found using GDC. Global Omega-Complexity appears to be a sensitive measure for subtle, central effects of chewing gum with and without flavor.

Effects of task modality, length and complexity on time for activities in lucid dreams

Introduction: Nocturnal dreams can be considered as a kind of simulation of the real world on a higher cognitive level (Erlacher & Schredl, 2008). Within lucid dreams, the dreamer is aware of the dream state and thus able to control the ongoing dream content. Previous studies could demonstrate that it is possible to practice motor tasks during lucid dreams and doing so improved performance while awake (Erlacher & Schredl, 2010). Even though lucid dream practice might be a promising kind of cognitive rehearsal in sports, little is known about the characteristics of actions in lucid dreams. The purpose of the present study was to explore the relationship between time in dreams and wakefulness because in an earlier study (Erlacher & Schredl, 2004) we found that performing squads took lucid dreamers 44.5 % more time than in the waking state while for counting the same participants showed no differences between dreaming and wakefulness. To find out if the task modality, the task length or the task complexity require longer times in lucid dreams than in wakefulness three experiments were conducted. Methods: In the first experiment five proficient lucid dreamers spent two to three non-consecutive nights in the sleep laboratory with polysomnographic recording to control for REM sleep and determine eye signals. Participants counted from 1-10, 1-20 and 1-30 in wakefulness and in their lucid dreams. While dreaming they marked onset of lucidity as well as beginning and end of the counting task with a Left-Right-Left-Right eye movement and reported their dreams after being awakened. The same procedure was used for the second experiment with seven lucid dreamers except that they had to walk 10, 20 or 30 steps. In the third experiment nine participants performed an exercise involving gymnastics elements such as various jumps and a roll. To control for length of the task the gymnastic exercise in the waking state lasted about the same time as walking 10 steps. Results: As a general result we found – as in the study before – that performing a task in the lucid dream requires more time than in wakefulness. This tendency was found for all three tasks. However, there was no difference for the task modality (counting vs. motor task). Also the relative time for the different lengths of the tasks showed no difference. And finally, the more complex motor task (gymnastic routine) did not require more time in lucid dreams than the simple motor task. Discussion/Conclusion: The results showed that there is a robust effect of time in lucid dreams compared to wakefulness. The three experiments could not explain that those differences are caused by task modality, task length or task complexity. Therefore further possible candidates needs to be investigated e.g. experience in lucid dreaming or psychological variables. References: Erlacher, D. & Schredl, M. (2010). Practicing a motor task in a lucid dream enhances subsequent performance: A pilot study. The Sport Psychologist, 24(2), 157-167. Erlacher, D. & Schredl, M. (2008). Do REM (lucid) dreamed and executed actions share the same neural substrate? International Journal of Dream Research, 1(1), 7-13. Erlacher, D. & Schredl, M. (2004). Time required for motor activity in lucid dreams. Perceptual and Motor Skills, 99, 1239-1242.

Impact of unlinked deaths and coding changes on mortality trends in the Swiss National Cohort

BACKGROUND Results of epidemiological studies linking census with mortality records may be affected by unlinked deaths and changes in cause of death classification. We examined these issues in the Swiss National Cohort (SNC). METHODS The SNC is a longitudinal study of the entire Swiss population, based on the 1990 (6.8 million persons) and 2000 (7.3 million persons) censuses. Among 1,053,393 deaths recorded 1991-2007 5.4% could not be linked using stringent probabilistic linkage. We included the unlinked deaths using pragmatic linkages and compared mortality rates for selected causes with official mortality rates. We also examined the impact of the 1995 change in cause of death coding from version 8 (with some additional rules) to version 10 of the International Classification of Diseases (ICD), using Poisson regression models with restricted cubic splines. Finally, we compared results from Cox models including and excluding unlinked deaths of the association of education, marital status, and nationality with selected causes of death. RESULTS SNC mortality rates underestimated all cause mortality by 9.6% (range 2.4%-17.9%) in the 85+ population. Underestimation was less pronounced in years nearer the censuses and in the 75-84 age group. After including 99.7% of unlinked deaths, annual all cause SNC mortality rates were reflecting official rates (relative difference between -1.4% and +1.8%). In the 85+ population the rates for prostate and breast cancer dropped, by 16% and 21% respectively, between 1994 and 1995 coincident with the change in cause of death coding policy. For suicide in males almost no change was observed. Hazard ratios were only negligibly affected by including the unlinked deaths. A sudden decrease in breast (21% less, 95% confidence interval: 12%-28%) and prostate (16% less, 95% confidence interval: 7%-23%) cancer mortality rates in the 85+ population coincided with the 1995 change in cause of death coding policy. CONCLUSIONS Unlinked deaths bias analyses of absolute mortality rates downwards but have little effect on relative mortality. To describe time trends of cause-specific mortality in the SNC, accounting for the unlinked deaths and for the possible effect of change in death certificate coding was necessary.

Specific and Nonspecific Psychological Interventions for PTSD Symptoms: A Meta-Analysis With Problem Complexity as a Moderator

CONTEXT The necessity of specific intervention components for the successful treatment of patients with posttraumatic stress disorder is the subject of controversy. OBJECTIVE To investigate the complexity of clinical problems as a moderator of relative effects between specific and nonspecific psychological interventions. METHODS We included 18 randomized controlled trials, directly comparing specific and nonspecific psychological interventions. We conducted moderator analyses, including the complexity of clinical problems as predictor. RESULTS Our results have confirmed the moderate superiority of specific over nonspecific psychological interventions; however, the superiority was small in studies with complex clinical problems and large in studies with noncomplex clinical problems. CONCLUSIONS For patients with complex clinical problems, our results suggest that particular nonspecific psychological interventions may be offered as an alternative to specific psychological interventions. In contrast, for patients with noncomplex clinical problems, specific psychological interventions are the best treatment option.

A non-coding genomic duplication at the HMX1 locus is associated with crop ears in highland cattle.

Highland cattle with congenital crop ears have notches of variable size on the tips of both ears. In some cases, cartilage deformation can be seen and occasionally the external ears are shortened. We collected 40 cases and 80 controls across Switzerland. Pedigree data analysis confirmed a monogenic autosomal dominant mode of inheritance with variable expressivity. All affected animals could be traced back to a single common ancestor. A genome-wide association study was performed and the causative mutation was mapped to a 4 Mb interval on bovine chromosome 6. The H6 family homeobox 1 (HMX1) gene was selected as a positional and functional candidate gene. By whole genome re-sequencing of an affected Highland cattle, we detected 6 non-synonymous coding sequence variants and two variants in an ultra-conserved element at the HMX1 locus with respect to the reference genome. Of these 8 variants, only a non-coding 76 bp genomic duplication (g.106720058_106720133dup) located in the conserved region was perfectly associated with crop ears. The identified copy number variation probably results in HMX1 misregulation and possible gain-of-function. Our findings confirm the role of HMX1 during the development of the external ear. As it is sometimes difficult to phenotypically diagnose Highland cattle with slight ear notches, genetic testing can now be used to improve selection against this undesired trait.

Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function

The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation.

A NEW TUMOR SUPPRESSOR GENE CANDIDATE REGULATED BY THE NON-CODING RNA PCA3 IN HUMAN PROSTATE CANCER

Prostate cancer is the second leading cause of cancer-related death and the most common non-skin cancer in men in the USA. Considerable advancements in the practice of medicine have allowed a significant improvement in the diagnosis and treatment of this disease and, in recent years, both incidence and mortality rates have been slightly declining. However, it is still estimated that 1 man in 6 will be diagnosed with prostate cancer during his lifetime, and 1 man in 35 will die of the disease. In order to identify novel strategies and effective therapeutic approaches in the fight against prostate cancer, it is imperative to improve our understanding of its complex biology since many aspects of prostate cancer initiation and progression still remain elusive. The study of tumor biomarkers, due to their specific altered expression in tumor versus normal tissue, is a valid tool for elucidating key aspects of cancer biology, and may provide important insights into the molecular mechanisms underlining the tumorigenesis process of prostate cancer. PCA3, is considered the most specific prostate cancer biomarker, however its biological role, until now, remained unknown. PCA3 is a long non-coding RNA (ncRNA) expressed from chromosome 9q21 and its study led us to the discovery of a novel human gene, PC-TSGC, transcribed from the opposite strand and in an antisense orientation to PCA3. With the work presented in this thesis, we demonstrate that PCA3 exerts a negative regulatory role over PC-TSGC, and we propose PC-TSGC to be a new tumor suppressor gene that contrasts the transformation of prostate cells by inhibiting Rho-GTPases signaling pathways. Our findings provide a biological role for PCA3 in prostate cancer and suggest a new mechanism of tumor suppressor gene inactivation mediated by non-coding RNA. Also, the characterization of PCA3 and PC-TSGC led us to propose a new molecular pathway involving both genes in the transformation process of the prostate, thus providing a new piece of the jigsaw puzzle representing the complex biology of prostate cancer.

Historical and idealized climate model experiments: an intercomparison of Earth system models of intermediate complexity

Both historical and idealized climate model experiments are performed with a variety of Earth system models of intermediate complexity (EMICs) as part of a community contribution to the Intergovernmental Panel on Climate Change Fifth Assessment Report. Historical simulations start at 850 CE and continue through to 2005. The standard simulations include changes in forcing from solar luminosity, Earth's orbital configuration, CO2, additional greenhouse gases, land use, and sulphate and volcanic aerosols. In spite of very different modelled pre-industrial global surface air temperatures, overall 20th century trends in surface air temperature and carbon uptake are reasonably well simulated when compared to observed trends. Land carbon fluxes show much more variation between models than ocean carbon fluxes, and recent land fluxes appear to be slightly underestimated. It is possible that recent modelled climate trends or climate–carbon feedbacks are overestimated resulting in too much land carbon loss or that carbon uptake due to CO2 and/or nitrogen fertilization is underestimated. Several one thousand year long, idealized, 2 × and 4 × CO2 experiments are used to quantify standard model characteristics, including transient and equilibrium climate sensitivities, and climate–carbon feedbacks. The values from EMICs generally fall within the range given by general circulation models. Seven additional historical simulations, each including a single specified forcing, are used to assess the contributions of different climate forcings to the overall climate and carbon cycle response. The response of surface air temperature is the linear sum of the individual forcings, while the carbon cycle response shows a non-linear interaction between land-use change and CO2 forcings for some models. Finally, the preindustrial portions of the last millennium simulations are used to assess historical model carbon-climate feedbacks. Given the specified forcing, there is a tendency for the EMICs to underestimate the drop in surface air temperature and CO2 between the Medieval Climate Anomaly and the Little Ice Age estimated from palaeoclimate reconstructions. This in turn could be a result of unforced variability within the climate system, uncertainty in the reconstructions of temperature and CO2, errors in the reconstructions of forcing used to drive the models, or the incomplete representation of certain processes within the models. Given the forcing datasets used in this study, the models calculate significant land-use emissions over the pre-industrial period. This implies that land-use emissions might need to be taken into account, when making estimates of climate–carbon feedbacks from palaeoclimate reconstructions.

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.

EVALUATION OF INTENSITY MODULATED RADIATION THERAPY (IMRT) DELIVERY ERROR DUE TO IMRT TREATMENT PLAN COMPLEXITY AND IMPROPERLY MATCHED DOSIMETRY DATA

Intensity modulated radiation therapy (IMRT) is a technique that delivers a highly conformal dose distribution to a target volume while attempting to maximally spare the surrounding normal tissues. IMRT is a common treatment modality used for treating head and neck (H&N) cancers, and the presence of many critical structures in this region requires accurate treatment delivery. The Radiological Physics Center (RPC) acts as both a remote and on-site quality assurance agency that credentials institutions participating in clinical trials. To date, about 30% of all IMRT participants have failed the RPC’s remote audit using the IMRT H&N phantom. The purpose of this project is to evaluate possible causes of H&N IMRT delivery errors observed by the RPC, specifically IMRT treatment plan complexity and the use of improper dosimetry data from machines that were thought to be matched but in reality were not. Eight H&N IMRT plans with a range of complexity defined by total MU (1460-3466), number of segments (54-225), and modulation complexity scores (MCS) (0.181-0.609) were created in Pinnacle v.8m. These plans were delivered to the RPC’s H&N phantom on a single Varian Clinac. One of the IMRT plans (1851 MU, 88 segments, and MCS=0.469) was equivalent to the median H&N plan from 130 previous RPC H&N phantom irradiations. This average IMRT plan was also delivered on four matched Varian Clinac machines and the dose distribution calculated using a different 6MV beam model. Radiochromic film and TLD within the phantom were used to analyze the dose profiles and absolute doses, respectively. The measured and calculated were compared to evaluate the dosimetric accuracy. All deliveries met the RPC acceptance criteria of ±7% absolute dose difference and 4 mm distance-to-agreement (DTA). Additionally, gamma index analysis was performed for all deliveries using a ±7%/4mm and ±5%/3mm criteria. Increasing the treatment plan complexity by varying the MU, number of segments, or varying the MCS resulted in no clear trend toward an increase in dosimetric error determined by the absolute dose difference, DTA, or gamma index. Varying the delivery machines as well as the beam model (use of a Clinac 6EX 6MV beam model vs. Clinac 21EX 6MV model), also did not show any clear trend towards an increased dosimetric error using the same criteria indicated above.

The long non-coding RNA NEAT1 is increased in IUGR placentas, leading to potential new hypotheses of IUGR origin/development.

INTRODUCTION Intrauterine Growth Restriction (IUGR) is a multifactorial disease defined by an inability of the fetus to reach its growth potential. IUGR not only increases the risk of neonatal mortality/morbidity, but also the risk of metabolic syndrome during adulthood. Certain placental proteins have been shown to be implicated in IUGR development, such as proteins from the GH/IGF axis and angiogenesis/apoptosis processes. METHODS Twelve patients with term IUGR pregnancy (birth weight < 10th percentile) and 12 CTRLs were included. mRNA was extracted from the fetal part of the placenta and submitted to a subtraction method (Clontech PCR-Select cDNA Subtraction). RESULTS One candidate gene identified was the long non-coding RNA NEAT1 (nuclear paraspeckle assembly transcript 1). NEAT1 is the core component of a subnuclear structure called paraspeckle. This structure is responsible for the retention of hyperedited mRNAs in the nucleus. Overall, NEAT1 mRNA expression was 4.14 (±1.16)-fold increased in IUGR vs. CTRL placentas (P = 0.009). NEAT1 was exclusively localized in the nuclei of the villous trophoblasts and was expressed in more nuclei and with greater intensity in IUGR placentas than in CTRLs. PSPC1, one of the three main proteins of the paraspeckle, co-localized with NEAT1 in the villous trophoblasts. The expression of NEAT1_2 mRNA, the long isoform of NEAT1, was only modestly increased in IUGR vs. CTRL placentas. DISCUSSION/CONCLUSION The increase in NEAT1 and its co-localization with PSPC1 suggests an increase in paraspeckles in IUGR villous trophoblasts. This could lead to an increased retention of important mRNAs in villous trophoblasts nuclei. Given that the villous trophoblasts are crucial for the barrier function of the placenta, this could in part explain placental dysfunction in idiopathic IUGR fetuses.

LINKAGE RELATIONSHIPS AMONG PROTEIN-CODING LOCI IN FISHES OF THE GENUS XIPHOPHORUS

Inbred strains of three species of fishes of the genus Xiphophorus (platyfish and swordtails) were crossed to produce intra- and interspecific F(,1) hybrids, which were then backcrossed to one or both parental stocks. Backcross hybrids were used for the analysis of segregation and linkage of 33 protein-coding loci (whose products were visualized by starch gel electrophoresis) and a sex-linked pigment pattern gene. Segregation was Mendelian for all loci with the exception of one instance of segregation distortion. Six linkage groups of enzyme-coding loci were established: LG I, ADA --6%-- G(,6)PD --24%-- 6PGD; LG II, Est-2 --27%-- Est-3 --0%-- Est-5 --23%-- LDH-1 --16%-- MPI; LG III, AcPh --38%-- G(,3)PD-1 (GUK-2 --14%-- G(,3)PD-1 is also in LG III, but the position of GUK-2 with respect to AcPh has not yet been determined); LG IV, GPI-1 --41%-- IDH-1; LG V, Est-1 --38%-- MDH-2; and LG VI, P1P --7%-- UMPK-1 (P1P is a plasma protein, very probably transferrin).^ Sex-specific recombination appeared absent in LG II and LG IV locus pairs; significantly higher male recombination was demonstrated in LG I but significantly higher female recombination was detected in LG V. Only one significant population-specific difference in recombination was detected, in the G(,6)PD - 6PGD region of LG I; the notable absence of such effects implies close correspondence of the genomes of the species used in the study. Two cases of possible evolutionary conservation of linkage groups in fishes and mammals were described, involving the G(,6)PD - 6PGD linkage in LG I and the cluster of esterase loci in LG II. One clear case of divergence was observed, that of the linkage of ADA in LG I. It was estimated that a minimum of (TURN)50% of the Xiphophorus genome was marked by the loci studied. Therefore, the prior probability that a new locus will assort independently from the markers already established is estimated to be less than 0.5. A maximum of 21 of the 24 pairs of chromosomes could be marked with at least one locus.^ Only the two LG V loci showed a significant association with a postulated gene controlling the severity of a genetically controlled melanoma caused by abnormal proliferation of macromelanophore pigment pattern cells. The independence of melanotic severity from all other informative markers implies that one or at most a few major genes are involved in control of melanotic severity in this system. ^