Impact of prenatal environmental stress on cortical development

Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: 1. molecular mechanisms shared by various types of environmental stressors, 2. the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and 3. interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders

Proteome dynamics during postnatal mouse corpus callosum development.

Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled amino acids in mammals (SILAM). The analyzed corpus callosi had distinct proteomic profiles depending on age, indicating rapid progression of specific molecular events during this period. The proteomic profiles were then segregated into five separate clusters, each with distinct trajectories relevant to their intended developmental functions. Our analysis both confirms many previously-identified proteins in aspects of corpus callosum development, and identifies new candidates in understudied areas of development including callosal axon refinement. We present a valuable resource for identifying new proteins integral to corpus callosum development that will provide new insights into the development and diseases afflicting this structure

On the Nature of AX J2049.6+2939 and AX J2050.0+2914

AX J2049.6+2939 is a compact X-ray source in the vicinity of the southern blow-up region of the Cygnus Loop supernova remnant (Miyata et al. 1998a). This source was the brightest X-ray source inside the Cygnus Loop observed during the ASCA survey project. The X-ray spectrum was well fitted by a power-law function with a photon index of $-2.1 \pm 0.1$. Short-term timing analysis was performed and no coherent pulsation was found. Follow-up observations with ASCA have revealed a large variation in X-ray intensity by a factor of $\simeq$ 50, whereas the spectral shape did not change within the statistical uncertainties. In the second ASCA observation, we found another X-ray source, AX J2050.0+2941, at the north east of AX J2049.6+2939. During the three ASCA observations, the X-ray intensity of AX J2050.0+2941 varied by a factor of $\simeq$4. No coherent pulsations could be found for AX J2050.0+2941. We have performed optical photometric and spectroscopic observations in the vicinity of AX J2049.6+2939 at the Kitt Peak National Observatory (KPNO). As a result, all objects brighter than $B$-band magnitude of 22 in the error box can be identified with normal stars. Combined with the X-ray results and the fact that there are no radio counterparts, AX J2049.6+2939 is not likely to be either an ordinary rotation-powered pulsar or an AGN. The nature of AX J2049.6+2939 is still unclear and further observations over a wide energy band are strongly required. As to AX J2050.0+2941, the long-term X-ray variability and the radio counterpart suggests that it is an AGN.Comment: 23 pages, 4 figures, Accepted for publication by Astrophysical Journa

Predictors of the Response to Tolvaptan Therapy and Its Effect on Prognosis in Cirrhotic Patients with Ascites

Aims: The vasopressin V2 receptor antagonist, tolvaptan, has been reported to be effective in cirrhotic patients with ascites. Here, we evaluated predictors of the response to tolvaptan. Methods: A total of 97 patients with cirrhosis (60 males; median age, 63 years) who had been treated for ascites with oral tolvaptan were enrolled. Tolvaptan efficacy was defined as urine volume increase of ≥500 mL or a urine volume ≥2000 mL/day on the day following treatment. Normalization of the serum sodium (Na) level after 1 week of treatment and the posttreatment survival rate was analyzed. Results: Tolvaptan therapy resulted in effective urination in 67% of patients. A multivariate analysis revealed that the blood urea nitrogen/creatinine (BUN/Cr) ratio and urinary Na/potassium (Na/K) ratio were predictive of the tolvaptan response (p <0.05). The serum Na level was 135 (121–145) mEq/L, and normal levels were recovered in 50.0% of the patients with an initial Na level of <135 mEq/L. The posttreatment survival rate was significantly higher in patients who responded to tolvaptan therapy (p <0.05). Conclusions: The combination of the initial BUN/Cr and urine Na/K ratios and a normalized serum Na level after 1 week was predictive of a favorable outcome to tolvaptan therapy

The X-ray CCD camera of the MAXI Experiment on the ISS/JEM

MAXI, Monitor of All-sky X-ray Image, is the X-ray observatory on the Japanese experimental module (JEM) Exposed Facility (EF) on the International Space Station (ISS). MAXI is a slit scanning camera which consists of two kinds of X-ray detectors: one is a one-dimensional position-sensitive proportional counter with a total area of $\sim 5000 cm^2$, the Gas Slit Camera (GSC), and the other is an X-ray CCD array with a total area $\sim 200 cm^2$, the Solid-state Slit Camera (SSC). The GSC subtends a field of view with an angular dimension of 1$^\circ\times 180^\circ$ while the SSC subtends a field of view with an angular dimension of 1$^\circ$ times a little less than 180$^\circ$. In the course of one station orbit, MAXI can scan almost the entire sky with a precision of 1$^\circ$ and with an X-ray energy range of 0.5-30 keV. We have developed the engineering model of CCD chips and the analogue electronics for the SSC. The energy resolution of EM CCD for Mn K$\alpha$ has a full-width at half maximum of $\simeq$ 182 eV. Readout noise is $\simeq$ 11 e^- rms.Comment: 10 pages, 4 figures Accepted for Nuclear Instruments and Method in Physics Researc

Factors associated with anxiety and depression in rheumatoid arthritis patients: a cross-sectional study

BACKGROUND: The management of anxiety and depression symptoms in rheumatoid arthritis (RA) patients is vital. Previous study findings on this topic are conflicting, and the topic remains to be thoroughly investigated. This study aimed to clarify the association of RA disease activity with anxiety and depression symptoms after controlling for physical disability, pain, and medication. METHODS: We conducted a cross-sectional study of RA patients from the XXX Rheumatoid Arthritis Management Alliance cohort. We assessed patients using the Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and Hospital Anxiety and Depression Scale (HADS). Anxiety and depression symptoms were defined by a HADS score ≥ 8. We analyzed the data using multivariable logistic regression analyses. RESULTS: Of 517 participants, 17.6% had anxiety symptoms and 27.7% had depression symptoms. The multivariable logistic regression analysis demonstrated that DAS28 was not independently associated with anxiety symptoms (odds ratio [OR] [95% confidence interval; CI] 0.93 [0.48-1.78]; p = 0.82) and depression symptoms (OR [95% CI] 1.45 [0.81-2.61]; p = 0.22). However, DAS28 patient global assessment (PtGA) severity was associated with anxiety symptoms (OR [95% CI] 1.15 [1.02-1.29]; p = 0.03) and depression symptoms (OR [95% CI] 1.21 [1.09-1.35]; p < 0.01). Additionally, HAQ-DI scores ≤ 0.5 were associated with anxiety symptoms (OR [95% CI] 3.51 [1.85-6.64]; p < 0.01) and depression symptoms (OR [95% CI] 2.65 [1.56-4.50]; p < 0.01). Patients using steroids were more likely to have depression than those not using steroids (OR [95% CI] 1.66 [1.03-2.67]; p = 0.04). CONCLUSIONS: No association was found between RA disease activity and anxiety and depression symptoms in the multivariable logistic regression analysis. Patients with high PtGA scores or HAQ-DI scores ≤ 0.5 were more likely to experience anxiety and depression symptoms, irrespective of disease activity remission status. Rather than focusing solely on controlling disease activity, treatment should focus on improving or preserving physical function and the patient's overall sense of well-being

Can we live on a D-brane? -- Effective theory on a self-gravitating D-brane --

We consider a D-brane coupled with gravity in type IIB supergravity on S^5 and derive the effective theory on the D-brane in two different ways, that is, holographic and geometrical projection methods. We find that the effective equations on the brane obtained by these methods coincide. The theory on the D-brane described by the Born-Infeld action is not like Einstein-Maxwell theory in the lower order of the gradient expansion, i.e., the Maxwell field does not appear in the theory. Thus the careful analysis and statement for cosmology on self-gravitating D-brane should be demanded in realistic models.Comment: 13 pages, accepted for publication in Physical Review

Intake frequency of vegetables or seafoods negatively correlates with disease activity of rheumatoid arthritis

Objective: To clarify the relationship between dietary habit and disease activity of rheumatoid arthritis (RA). Methods: This study enrolled RA patients who met the ACR/EULAR 2010 classification criteria from Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort in 2015. 22-item food frequency questionnaire (FFQ) was taken for the measurement of dietary habit in a single-institution cohort of RA (Kyoto University Rheumatoid Arthritis Management Alliance: KURAMA) in 2015. The disease activities of RA using the Disease Activity Score calculated based on the erythrocyte sedimentation rate (DAS28-ESR), Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire (HAQ), and serum matrix metalloproteinase-3 (MMP-3) level, the use of disease-modifying anti-rheumatic drugs (DMARDs), disease duration, rheumatoid factor, anti-cyclic citrullinated antibody, and body mass index were also examined. All of them were combined and statistically analyzed. Results: 441 RA patients (81% women; mean age 65 years; mean disease duration 15 years) were enrolled from the KURAMA cohort. Average Disease Activity Score-28 using the erythrocyte sedimentation rate (DAS28-ESR) was 2.7. Univariate analysis showed that intake frequency of vegetables had a statistically significant negative correlation with disease activity markers, such as DAS28-ESR (ρ = −0.11, p<0.01), Simplified Disease Activity Index (SDAI) (ρ = −0.16, p<0.001), matrix metalloproteinase-3 (MMP-3) (ρ = −0.21, p<0.0001), and Health Assessment Questionnaire (HAQ) (ρ = −0.13, p<0.01). Factor analysis with varimax rotation was done to simplify the relevance of disease activity to various food items. 22 foods were categorized into five dietary patterns: “seafoods”, “vegetables/fruits”, “meats/fried foods”, “snacks”, and “processed foods”. The multivariate analysis adjusted for clinically significant confounders showed that “seafoods” had statistically significant negative correlations with DAS28-ESR (β = −0.15, p<0.01), SDAI (β = −0.18, p<0.001), MMP-3 (β = −0.15, p<0.01), and HAQ (β = −0.24, p<0.0001). “Vegetables/fruits” had statistically significant negative correlations with SDAI (β = −0.11 p<0.05), MMP-3 (β = −0.12, p<0.01), and HAQ (β = −0.11, p<0.05) Conclusions: These results suggest that high intake frequency of vegetables/fruits and/or seafoods might correlate with low disease activity

Have we already detected astrophysical symptoms of space-time noncommutativity ?

We discuss astrophysical implications of $\kappa$-Minkowski space-time, in which there appears space-time noncommutativity. We first derive a velocity formula for particles based on the motion of a wave packet. The result is that a massless particle moves at a constant speed as in the usual Minkowski space-time, which implies that an arrival time analysis by $\gamma$-rays from Markarian (Mk) 421 does not exclude space-time noncommutativity. Based on this observation, we analyze reaction processes in $\kappa$-Minkowski space-time which are related to the puzzling detections of extremely high-energy cosmic rays above the Greisen-Zatsepin-Kuzmin cutoff and of high-energy ($\sim$20 TeV) $\gamma$-rays from Mk 501.Comment: 10 pages, 6 figures, submitted to PRD, corrected some mistake