On-Orbit Results of Photoelectron Current Measurement System in Low Earth Orbit on HORYU-IV Satellite

On-orbit photoelectron current experiment is one of the missions carried out with the less resource available from a HORYU-IV satellite, for measuring the current from metallic and insulator surfaces from air mass zero (AMO) spectrum. This is with the view to determined photoelectron potential of materials widely used in spacecraft in space. HORYU-IV also known as Arc Event Generator and Investigator satellite (AEGIS) is among HORYU satellite series of Kyushu Institute of Technology, which was launched on February 17, 2016 as a piggy-back on-board H-IIA rocket. The measurement system consists of current-voltage amplifier circuits for Au, Kapton and Black Kapton samples with varying gains and other discrete components. We present the analysis of the telemetry data obtained after the launch; validate the effectiveness of the design and verification processes. The results show that the current measured from Black kapton sample surface had 1.80 nA and 2.70 nA, corresponds to 69.1ᵒ and 75.1ᵒ minimum and maximum elevation angles respectively. This paper described the on-orbit result of PEC and its verification through ground tests

Phorbol 12,13-Dibutyrate-Induced, Protein Kinase C-Mediated Contraction of Rabbit Bladder Smooth Muscle

Contraction of bladder smooth muscle is predominantly initiated by M3 muscarinic receptor-mediated activation of the Gq/11-phospholipase C β-protein kinase C (PKC) and the G12/13-RhoGEF-Rho kinase (ROCK) pathways. However, these pathways and their downstream effectors are not well understood in bladder smooth muscle. We used phorbol 12,13-dibutyrate (PDBu), and 1,2-dioctanoyl-sn-glycerol (DOG), activators of PKC, in this investigation. We were interested in dissecting the role(s) of PKC and to clarify the signaling pathways in bladder smooth muscle contraction, especially the potential cross-talk with ROCK and their downstream effectors in regulating myosin light chain phosphatase activity and force. To achieve this goal, the study was performed in the presence or absence of the PKC inhibitor bisindolylmaleimide-1 (Bis) or the ROCK inhibitor H-1152. Phosphorylation levels of Thr38-CPI-17 and Thr696/Thr850 myosin phosphatase target subunit (MYPT1) were measured during PDBu or DOG stimulation using site specific antibodies. PDBu-induced contraction in bladder smooth muscle involved both activation of PKC and PKC-dependent activation of ROCK. CPI-17 as a major downstream effector, is phosphorylated by PKC and ROCK during PDBu and DOG stimulation. Our results suggest that Thr696 and Thr850-MYPT1 phosphorylation are not involved in the regulation of a PDBu-induced contraction. The results also demonstrate that bladder smooth muscle contains a constitutively active isoform of ROCK that may play an important role in the regulation of bladder smooth muscle basal tone. Together with the results from our previous study, we developed a working model to describe the complex signaling pathways that regulate contraction of bladder smooth muscle

Chronic Post-Concussion Neurocognitive Deficits. II. Relationship with Persistent Symptoms

Individuals who sustain a concussion may continue to experience problems long after their injury. However, it has been postulated in the literature that the relationship between a concussive injury and persistent complaints attributed to it is mediated largely by the development of symptoms associated with posttraumatic stress disorder and depression. We sought to characterize cognitive deficits of adult patients who had persistent symptoms after a concussion and determine whether the original injury retains associations with these deficits after accounting for the developed symptoms that overlap with posttraumatic stress disorder and depression. We compared the results of neurocognitive testing from 33 patients of both genders aged 18-55 at three months to five years post-injury with those from 140 control subjects. Statistical comparisons revealed that patients generally produced accurate responses on reaction time-based tests, but with reduced efficiency. On visual tracking, patients increased gaze position error variability following an attention demanding task, an effect that may reflect greater fatigability. When neurocognitive performance was examined in the context of demographic- and symptom-related variables, the original injury retained associations with reduced performance at a statistically significant level. For some patients, reduced cognitive efficiency and fatigability may represent key elements of interference when interacting with the environment, leading to varied paths of recovery after a concussion. Poor recovery may be better understood when these deficits are taken into consideration

The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders

The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD

Pathway-Wide Association Study Implicates Multiple Sterol Transport and Metabolism Genes in HDL Cholesterol Regulation

Pathway-based association methods have been proposed to be an effective approach in identifying disease genes, when single-marker association tests do not have sufficient power. The analysis of quantitative traits may be benefited from these approaches, by sampling from two extreme tails of the distribution. Here we tested a pathway association approach on a small genome-wide association study (GWAS) on 653 subjects with extremely high high-density lipoprotein cholesterol (HDL-C) levels and 784 subjects with low HDL-C levels. We identified 102 genes in the sterol transport and metabolism pathways that collectively associate with HDL-C levels, and replicated these association signals in an independent GWAS. Interestingly, the pathways include 18 genes implicated in previous GWAS on lipid traits, suggesting that genuine HDL-C genes are highly enriched in these pathways. Additionally, multiple biologically relevant loci in the pathways were not detected by previous GWAS, including genes implicated in previous candidate gene association studies (such as LEPR, APOA2, HDLBP, SOAT2), genes that cause Mendelian forms of lipid disorders (such as DHCR24), and genes expressing dyslipidemia phenotypes in knockout mice (such as SOAT1, PON1). Our study suggests that sampling from two extreme tails of a quantitative trait and examining genetic pathways may yield biological insights from smaller samples than are generally required using single-marker analysis in large-scale GWAS. Our results also implicate that functionally related genes work together to regulate complex quantitative traits, and that future large-scale studies may benefit from pathway-association approaches to identify novel pathways regulating HDL-C levels

In vivo function and comparative genomic analyses of the Drosophila gut microbiota identify candidate symbiosis factors

Symbiosis is often characterized by co-evolutionary changes in the genomes of the partners involved. An understanding of these changes can provide insight into the nature of the relationship, including the mechanisms that initiate and maintain an association between organisms. In this study we examined the genome sequences of bacteria isolated from the Drosophila melanogaster gut with the objective of identifying genes that are important for function in the host. We compared microbiota isolates with con-specific or closely related bacterial species isolated from non-fly environments. First the phenotype of germ-free Drosophila (axenic flies) was compared to that of flies colonized with specific bacteria (gnotobiotic flies) as a measure of symbiotic function. Non-fly isolates were functionally distinct from bacteria isolated from flies, conferring slower development and an altered nutrient profile in the host, traits known to be microbiota-dependent. Comparative genomic methods were next employed to identify putative symbiosis factors: genes found in bacteria that restore microbiota-dependent traits to gnotobiotic flies, but absent from those that do not. Factors identified include riboflavin synthesis and stress resistance. We also used a phylogenomic approach to identify protein coding genes for which fly-isolate sequences were more similar to each other than to other sequences, reasoning that these genes may have a shared function unique to the fly environment. This method identified genes in Acetobacter species that cluster in two distinct genomic loci: one predicted to be involved in oxidative stress detoxification and another encoding an efflux pump. In summary, we leveraged genomic and in vivo functional comparisons to identify candidate traits that distinguish symbiotic bacteria. These candidates can serve as the basis for further work investigating the genetic requirements of bacteria for function and persistence in the Drosophila gut

Regular Multivitamin Supplement Use, Single Nucleotide Polymorphisms in ATIC, SHMT2, and SLC46A1, and Risk of Ovarian Carcinoma

ATIC, SHMT2, and SLC46A1 have essential roles in one-carbon (1-C) transfer. The authors examined whether associations between ovarian carcinoma and 15 variants in these genes are modified by regular multivitamin use, a source of 1-C donors, among Caucasian participants from two US case–control studies. Using a phased study design, variant-by-multivitamin interactions were tested, and associations between variants and ovarian carcinoma were reported stratified by multivitamin supplement use. Per-allele risk associations were modified by multivitamin use at six variants among 655 cases and 920 controls (Phase 1). In a larger sample of 968 cases and 1,265 controls (Phases 1 and 2), interactions were significant (P ≤ 0.03) for two variants, particularly among regular multivitamin users: ATIC rs7586969 [odds ratio (OR) = 0.7, 95% confidence interval (CI) = 0.6–0.9] and ATIC rs16853834 (OR = 1.5, 95% CI = 1.1–2.0). The two ATIC single nucleotide polymorphisms (SNPs) did not share the same haplotype; however, the haplotypes they comprised mirrored their SNP risk associations among regular multivitamin supplement users. A multi-variant analysis was also performed by comparing the observed likelihood ratio test statistic from adjusted models with and without the two ATIC variant-by-multivitamin interaction terms with a null distribution of test statistics generated by permuting case status 10,000 times. The corresponding observed P value of 0.001 was more extreme than the permutation-derived P value of 0.009, suggesting rejection of the null hypothesis of no association. In summary, there is little statistical evidence that the 15 variants are independently associated with risk of ovarian carcinoma. However, the statistical interaction of ATIC variants with regular multivitamin intake, when evaluated at both the SNP and gene level, may support these findings as relevant to ovarian health and disease processes

A Tool for Interactive Data Visualization: Application to Over 10,000 Brain Imaging and Phantom MRI Data Sets

In this paper we propose a web-based approach for quick visualization of big data from brain magnetic resonance imaging (MRI) scans using a combination of an automated image capture and processing system, nonlinear embedding, and interactive data visualization tools. We draw upon thousands of MRI scans captured via the COllaborative Imaging and Neuroinformatics Suite (COINS). We then interface the output of several analysis pipelines based on structural and functional data to a t-distributed stochastic neighbor embedding (t-SNE) algorithm which reduces the number of dimensions for each scan in the input data set to two dimensions while preserving the local structure of data sets. Finally, we interactively display the output of this approach via a web-page, based on data driven documents (D3) JavaScript library. Two distinct approaches were used to visualize the data. In the first approach, we computed multiple quality control (QC) values from pre-processed data, which were used as inputs to the t-SNE algorithm. This approach helps in assessing the quality of each data set relative to others. In the second case, computed variables of interest (e.g., brain volume or voxel values from segmented gray matter images) were used as inputs to the t-SNE algorithm. This approach helps in identifying interesting patterns in the data sets. We demonstrate these approaches using multiple examples from over 10,000 data sets including (1) quality control measures calculated from phantom data over time, (2) quality control data from human functional MRI data across various studies, scanners, sites, (3) volumetric and density measures from human structural MRI data across various studies, scanners and sites. Results from (1) and (2) show the potential of our approach to combine t-SNE data reduction with interactive color coding of variables of interest to quickly identify visually unique clusters of data (i.e., data sets with poor QC, clustering of data by site) quickly. Results from (3) demonstrate interesting patterns of gray matter and volume, and evaluate how they map onto variables including scanners, age, and gender. In sum, the proposed approach allows researchers to rapidly identify and extract meaningful information from big data sets. Such tools are becoming increasingly important as datasets grow larger

Variation in Onset of Leaf Unfolding and Wood Formation in a Central African Tropical Tree Species

A diversity of phenological strategies has been reported for tropical tree species. Defoliation and seasonal dormancy of cambial activity inform us on how trees cope with water stress during the dry season, or maximize the use of resources during the rainy season. Here, we study the matching between leaf phenology (unfolding and shedding) and cambial activity for Prioria balsamifera, a key timber species in the Democratic Republic of Congo. In particular, we (i) evaluated the seasonality of cambial activity and synchrony of phenology among trees in response to climate and (ii) identified the seasonality of leaf phenology and its relation with cambial phenology. The study was conducted in the Luki Man and Biosphere Reserve, located in the Mayombe forest at the southern margin of the Congo Basin. Historic defoliation data were collected every ten days using weekly crown observations whereas recent observations involved timelapse cameras. Cambial pinning was performed on ten trees during 20 months and radius dendrometers were installed on three trees during 13 months. Tree rings were measured on cores from 13 trees and growth synchrony was evaluated. We found that P. balsamifera defoliates annually with a peak observed at the end of the dry season and the beginning of the rainy season. The new leaves unfolded shortly after shedding of the old leaves. The peak defoliation dates varied across years from September 12 to November 14 and the fraction of number of trees that defoliated at a given time was found to be negatively correlated with annual rainfall and temperature; during the dry season, when precipitation and temperatures are the lowest. Wood formation (radial growth), was found to be highly seasonal, with cambial dormancy occurring during the dry season and growth starting at the beginning of the rainy season. Individual ringwidth series did not cross date well. The within species variability of leaf phenology and cambial rhythms provides indication about resistance of the population against climatic changes

Loss of Sustained Activity in the Ventromedial Prefrontal Cortex in Response to Repeated Stress in Individuals with Early-Life Emotional Abuse: Implications for Depression Vulnerability

Repeated psychosocial stress in early life has significant impact on both behavior and neural function which, together, increase vulnerability to depression. However, neural mechanisms related to repeated stress remain unclear. We hypothesize that early-life stress may result in a reduced capacity for cognitive control in response to a repeated stressor, particularly in individuals who developed maladaptive emotional processing strategies, namely trait rumination. Individuals who encountered early-life stress but have adaptive emotional processing, namely trait mindfulness, may demonstrate an opposite pattern. Using a mental arithmetic task to induce mild stress and a mindful breathing task to induce a mindful state, we tested this hypothesis by examining blood perfusion changes over time in healthy young men. We found that subjects with early-life stress, particularly emotional abuse, failed to sustain neural activation in the orbitofrontal and ventromedial prefrontal cortex (vmPFC) over time. Given that the vmPFC is known to regulate amygdala activity during emotional processing, we subsequently compared the perfusion in the vmPFC and the amygdala in depression-vulnerable (having early life stress and high in rumination) and resilient (having early life stress and high in mindfulness) subjects. We found that depression-vulnerable subjects had increased amygdala perfusion and reduced vmPFC perfusion during the later runs than that during the earlier stressful task runs. In contrast, depression resilient individuals showed the reverse pattern. Our results indicate that the vmPFC of depression-vulnerable subjects may have a limited capacity to inhibit amygdala activation to repeated stress over time, whereas the vmPFC in resilient individuals may adapt to stress quickly. This pilot study warrants future investigation to clarify the stress-related neural activity pattern dynamically to identify depression vulnerability at an individual level