Genomic and neuroimaging approaches to bipolar disorder

BACKGROUND: To date, besides genome-wide association studies, a variety of other genetic analyses (e.g. polygenic risk scores, whole-exome sequencing and whole-genome sequencing) have been conducted, and a large amount of data has been gathered for investigating the involvement of common, rare and very rare types of DNA sequence variants in bipolar disorder. Also, non-invasive neuroimaging methods can be used to quantify changes in brain structure and function in patients with bipolar disorder. AIMS: To provide a comprehensive assessment of genetic findings associated with bipolar disorder, based on the evaluation of different genomic approaches and neuroimaging studies. METHOD: We conducted a PubMed search of all relevant literatures from the beginning to the present, by querying related search strings. RESULTS: ANK3, CACNA1C, SYNE1, ODZ4 and TRANK1 are five genes that have been replicated as key gene candidates in bipolar disorder pathophysiology, through the investigated studies. The percentage of phenotypic variance explained by the identified variants is small (approximately 4.7%). Bipolar disorder polygenic risk scores are associated with other psychiatric phenotypes. The ENIGMA-BD studies show a replicable pattern of lower cortical thickness, altered white matter integrity and smaller subcortical volumes in bipolar disorder. CONCLUSIONS: The low amount of explained phenotypic variance highlights the need for further large-scale investigations, especially among non-European populations, to achieve a more complete understanding of the genetic architecture of bipolar disorder and the missing heritability. Combining neuroimaging data with genetic data in large-scale studies might help researchers acquire a better knowledge of the engaged brain regions in bipolar disorder

Changes in lipid distribution in E. coli strains in response to norfloxacin

Bacterial resistance to antibiotics has become an increasing threat, requiring not only the development of new targets in drug discovery, but more importantly, a better understanding of cellular response. In the current study, three closely related Escherichia coli strains, a wild type (MG1655), and an isogenic pair derived from the wild type (DPB635 and DPB636) are studied following exposure to sub lethal concentrations of antibiotic (norfloxacin) over time. In particular, genotype similarities between the three strains were assessed based on the lipid regulation response (e.g., presence/absence and up/down regulation). Lipid identification was performed using direct surface probe analysis (Matrix-assisted laser desorption/ionization, MALDI), coupled to high-resolution mass spectrometry (Fourier transform ion cyclotron resonance mass spectrometry, FT-ICR MS) followed by statistical analysis of variability and reproducibility across batches using internal standards. Inspection of the lipid profile showed that for the MG1655, DPB635 and DPB636 E. coli strains, a similar distribution of the altered lipids were observed after exposure to norfloxacin antibiotic (e.g., fatty acids and glycerol phospholipids are up and down regulated, respectively). Additionally, variations in the lipid distribution resemble the extent to which each strain can combat the antibiotic exposure. That is, the topA66 topoisomerase I mutation of DPB636 translates into diminished response related to antibiotic sensitivity when compared to MG1655 and the DPB635 strains

Presentation and Outcomes After Medical and Surgical Treatment Versus Medical Treatment Alone of Spontaneous Infectious Spondylodiscitis: A Systematic Literature Review and Meta-Analysis.

Study Design: Systematic literature review. Objectives: The aims of this study were to (1) describe the clinical features, disabilities, and incidence of neurologic deficits of pyogenic spondylodiscitis prior to treatment and (2) compare the functional outcomes between patients who underwent medical treatment alone or in combination with surgery for pyogenic spondylodiscitis. Methods: A systematic literature review was performed using PubMed according to PRISMA guidelines. No year restriction was put in place. Statistical analysis of pooled data, when documented in the original report (ie, number of patients with desired variable and number of patients evaluated), was conducted to determine the most common presenting symptoms, incidence of pre- and postoperative neurologic deficits, associated comorbidities, infectious pathogens, approach for surgery when performed, and duration of hospitalization. Outcomes data, including return to work status, resolution of back pain, and functional recovery were also pooled among all studies and surgery-specific studies alone. Meta-analysis of studies with subgroup analysis of pain-free outcome in surgical and medical patients was performed. Results: Fifty of 1286 studies were included, comprising 4173 patients undergoing either medical treatment alone or in combination with surgery. Back pain was the most common presenting symptom, reported in 91% of patients. Neurologic deficit was noted in 31% of patients. Conclusion: Medical management remains first-line treatment of infectious pyogenic spondylodiscitis. Surgery may be indicated for progressive pain, persistent infection on imaging, deformity or neurologic deficits. If surgery is required, reported literature shows potential for significant pain reduction, improved neurologic function and a high number of patients returning to a normal functional/work status

RNA interference of endochitinases in the sugarcane endophyte Trichoderma virens 223 reduces its fitness as a biocontrol agent of pineapple disease

publication-status: PublishedThe sugarcane root endophyte Trichoderma virens 223 holds enormous potential as a sustainable alternative to chemical pesticides in the control of sugarcane diseases. Its efficacy as a biocontrol agent is thought to be associated with its production of chitinase enzymes, including N-acetyl-β-D-glucosaminidases, chitobiosidases and endochitinases. We used targeted gene deletion and RNA-dependent gene silencing strategies to disrupt N-acetyl-β-D-glucosaminidase and endochitinase activities of the fungus, and to determine their roles in the biocontrol of soil-borne plant pathogens. The loss of N-acetyl-β-D-glucosaminidase activities was dispensable for biocontrol of the plurivorous damping-off pathogens Rhizoctonia solani and Sclerotinia sclerotiorum, and of the sugarcane pathogen Ceratocystis paradoxa, the causal agent of pineapple disease. Similarly, suppression of endochitinase activities had no effect on R. solani and S. sclerotiorum disease control, but had a pronounced effect on the ability of T. virens 223 to control pineapple disease. Our work demonstrates a critical requirement for T. virens 223 endochitinase activity in the biocontrol of C. paradoxa sugarcane disease, but not for general antagonism of other soil pathogens. This may reflect its lifestyle as a sugarcane root endophyte

Implementation of Brain Breaks((R)) in the Classroom and Effects on Attitudes toward Physical Activity in a Macedonian School Setting

The purpose of this study was to explore the effects of Brain Break((R)) activities on interest and motivation for physical activity among schoolchildren and the contribution of such activities on learning for health and holistic development. The study sample was comprised of 283 participants, primary school students from 3rd to 5th grades from two public schools in the Republic of Macedonia. Six experimental and six control groups were included in the study. Interventions in classroom settingsbased Brain Break((R)) video exercises were introduced in the experimental group during a period of three months. Students\u27 attitudes toward physical activity were tested using a self-report survey instrument entitled Attitudes toward Physical Activity Scale (APAS) before and after intervention. Applied factor analyses were completed and the results of these analysis support APAS validity and the successful use of this application in the measurement of the learning experience, self-awareness, self-efficacy, and self-confidence in developing physical fitness. Learning was enhanced by using video exercises. Information presented in this paper is meaningful for the promotion of better exercise habits and the holistic approach to better health by using personal motivation and motivation provided by others. The results from repeated ANCOVA suggest positive effects of the applied Brain Break((R)) video exercises as an interventional program. The study confirms the effect of application of Brain Break((R)) video exercises on children\u27s attitudes for physical activity, motivation for PA, internalization of movement habits as personal good

Acoustic intensity fluctuations induced by South China Sea internal tides and solitons

Author Posting. © IEEE, 2004. This article is posted here by permission of IEEE for personal use, not for redistribution. The definitive version was published in IEEE Journal of Oceanic Engineering 29 (2004): 1249-1263, doi:10.1109/JOE.2004.834173.Between late April and May 23, 2001, a suite of acoustic and oceanographic sensors was deployed by a team of U.S., Taiwan, and Singapore scientists in the northeastern South China Sea to study the effects of ocean variability on low-frequency sound propagation in a shelfbreak environment. The primary acoustic receiver was an L-shaped hydrophone array moored on the continental shelf that monitored a variety of signals transmitted along and across the shelfbreak by moored sources. This paper discusses and contrasts the fluctuations in the 400-Hz signals transmitted across the shelfbreak and measured by the vertical segment of the listening array on two different days, one with the passage of several huge solitons that depressed the shallow isotherms to near the sea bottom and one with a much less energetic internal wavefield. In addition to exhibiting large and rapid temporal changes, the acoustic data show a much more vertically diffused sound intensity field as the huge solitons occupied and passed through the transmission path. Using a space-time continuous empirical sound-speed model based on the moored temperature records, the observed acoustic intensity fluctuations are explained using coupled-mode physics.This work was supported by the U.S. Office of Naval Research

Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

Malalties; GenèticaEnfermedades; GenéticaDiseases; GeneticsGenomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures

The Impact of Brain Breaks Classroom-Based Physical Activities on Attitudes toward Physical Activity in Polish School Children in Third to Fifth Grade

The purpose of this study was to examine the effectiveness of the Brain Breaks® Physical Activity Solutions in changing attitudes toward physical activity of school children in a community in Poland. In 2015, a sample of 326 pupils aged 9–11 years old from 19 classes at three selected primary schools were randomly assigned to control and experimental groups within the study. During the classes, children in the experimental group performed physical activities two times per day in three to five minutes using Brain Breaks® videos for four months, while the control group did not use the videos during the test period. Students’ attitudes toward physical activities were assessed before and after the intervention using the “Attitudes toward Physical Activity Scale”. Repeated measures of ANOVA were used to examine the change from pre- to post-intervention. Overall, a repeated measures ANOVA indicated time-by-group interaction effects in ‘Self-efficacy on learning with video exercises’, F(1.32) = 75.28, p = 0.00, η2 = 0.19. Although the changes are minor, there were benefits of the intervention. It may be concluded that HOPSports Brain Breaks® Physical Activity Program contributes to better self-efficacy on learning while using video exercise of primary school children

Use of Intuitive Tools to Enhance Student Learning and User Experience

Most user interfaces today present system functions by use of verbal or iconic symbols on static 2D menu pages organized in a hierarchical system. This is unnatural to all human beings and must be learned, thus being a barrier between the full use and understanding of computer systems. With this problem in mind we set out to build a website and collaborative application for International Children's Center (ICC) which could be used not only across languages but across ages as well. This effort was tested on a daily basis by a multinational team consisting of students from the United States and Turkey as well as children from the respective countries. This attention to usability will not only lead to an intuitive tool for the client but also teach the students in the course how to build intuitive user interfaces

Attention Drives Synchronization of Alpha and Beta Rhythms between Right Inferior Frontal and Primary Sensory Neocortex

The right inferior frontal cortex (rIFC) is specifically associated with attentional control via the inhibition of behaviorally irrelevant stimuli and motor responses. Similarly, recent evidence has shown that alpha (7–14 Hz) and beta (15–29 Hz) oscillations in primary sensory neocortical areas are enhanced in the representation of non-attended stimuli, leading to the hypothesis that allocation of these rhythms plays an active role in optimal inattention. Here, we tested the hypothesis that selective synchronization between rIFC and primary sensory neocortex occurs in these frequency bands during inattention. We used magnetoencephalography to investigate phase synchrony between primary somatosensory (SI) and rIFC regions during a cued-attention tactile detection task that required suppression of response to uncertain distractor stimuli. Attentional modulation of synchrony between SI and rIFC was found in both the alpha and beta frequency bands. This synchrony manifested as an increase in the alpha-band early after cue between non-attended SI representations and rIFC, and as a subsequent increase in beta-band synchrony closer to stimulus processing. Differences in phase synchrony were not found in several proximal control regions. These results are the first to reveal distinct interactions between primary sensory cortex and rIFC in humans and suggest that synchrony between rIFC and primary sensory representations plays a role in the inhibition of irrelevant sensory stimuli and motor responses.National Institutes of Health (U.S.) (Grant P41RR14075)National Institutes of Health (U.S.) (Grant K25MH072941)National Institutes of Health (U.S.) (Grant K01AT003459)National Institutes of Health (U.S.) (Grant K24AT004095)National Institutes of Health (U.S.) (Grant RO1-NS045130-01)National Institutes of Health (U.S.) (Grant T32GM007484)National Science Foundation (U.S.) (Grant 0316933)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant DGE-1147470