Angular Distribution of γ\gamma-rays from Neutron-Induced Compound States of 140^{140}La

Angular distribution of individual $\gamma$-rays, emitted from a neutron-induced compound nuclear state via radiative capture reaction of ${}^{139}$La(n,$\gamma$) has been studied as a function of incident neutron energy in the epithermal region by using germanium detectors. An asymmetry $A_{\mathrm{LH}}$ was defined as $(N_{\mathrm L}-N_{\mathrm H})/(N_{\mathrm L}+N_{\mathrm H})$, where $N_{\mathrm L}$ and $N_{\mathrm H}$ are integrals of low and high energy region of a neutron resonance respectively, and we found that $A_{\mathrm{LH}}$ has the angular dependence of $(A\cos\theta_\gamma+B)$, where $\theta_\gamma$ is emitted angle of $\gamma$-rays, with $A= -0.3881\pm0.0236$ and $B=-0.0747\pm0.0105$ in 0.74 eV p-wave resonance. This angular distribution was analyzed within the framework of interference between s- and p-wave amplitudes in the entrance channel to the compound nuclear state, and it is interpreted as the value of the partial p-wave neutron width corresponding to the total angular momentum of the incident neutron combined with the weak matrix element, in the context of the mechanism of enhanced parity-violating effects. Additionally we used the result to quantify the possible enhancement of the breaking of the time-reversal invariance in the vicinity of the p-wave resonance.Comment: 14pages, 25 figure

Sex-Dependent Effects of Intestinal Microbiome Manipulation in a Mouse Model of Alzheimer’s Disease

Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex differences in the effects of oral probiotic, antibiotics, and synbiotic treatments in the AppNL-G-F mouse model of AD. The fecal microbiome demonstrated significant correlations between bacterial genera in AppNL-G-F mice and Aβ plaque load, gliosis, and memory performance. Female and not male AppNL-G-F mice fed probiotic but not synbiotic exhibited a decrease in Aβ plaques, microgliosis, brain TNF-α, and memory improvement compared to no treatment controls. Although antibiotics treatment did not produce these multiple changes in brain cytokines, memory, or gliosis, it did decrease Aβ plaque load and colon cytokines in AppNL-G-F males. The intestinal cytokine milieu and splenocyte phenotype of female but not male AppNL-G-F mice indicated a modest proinflammatory innate response following probiotic treatment compared to controls, with an adaptive response following antibiotics treatment in male AppNL-G-F mice. Overall, these results demonstrate the beneficial effects of probiotic only in AppNL-G-F females, with minimal benefits of antibiotics or synbiotic feeding in male or female mice

Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells

Capsaicin has known pharmacological effects including the ability to reversibly open cellular tight junctions, among others. The aim of this study was to develop a strategy to enhance the paracellular transport of a substance with low permeability (FITC-dextran) across an epithelial cell monolayer via reversible opening of cellular tight junctions using a nanosystem comprised by capsaicin and of chitosan. We compared the biophysical properties of free capsaicin and capsaicin-loaded chitosan nanocapsules, including their cytotoxicity towards epithelial MDCK-C7 cells and their effect on the integrity of tight junctions, membrane permeability and cellular uptake. The cytotoxic response of MDCK-C7 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, is not observable following its encapsulation. The interaction between nanocapsules and the tight junctions of MDCK-C7 cells was investigated by impedance spectroscopy, digital holographic microscopy and structured illumination fluorescence microscopy. The nanocapsules modulated the interaction between capsaicin and tight junctions as shown by the different time profile of trans-epithelial electrical resistance and the enhanced permeability of monolayers incubated with FITC-dextran. Structured illumination fluorescence microscopy showed that the nanocapsules were internalized by MDCK-C7 cells. The capsaicin-loaded nanocapsules could be further developed as drug nanocarriers with enhanced epithelial permeability

The utility of superficial abdominal reflex in the initial diagnosis of scoliosis: a retrospective review of clinical characteristics of scoliosis with syringomyelia

<p>Abstract</p> <p>Background</p> <p>With increasing use of magnetic resonance imaging (MRI), underlying syringomyelia is increasingly found in patients with presumed idiopathic scoliosis. To determine the indications for MRI in the differential diagnosis of scoliosis, several clinical characteristics of syringomyelia have been reported. Neurological signs, particularly abnormal superficial abdominal reflex (SAR), are important in establishing the initial diagnosis of scoliosis. However, the prevalence of abnormal SAR in patients with scoliosis and the sensitivity of this sign in predicting syringomyelia are not well known. We aimed to determine the diagnostic utility of SAR and other characteristics of syringomyelia in patients with scoliosis.</p> <p>Methods</p> <p>We reviewed the medical records of 93 patients with scoliosis, 90 of whom underwent corrective surgery. All patients underwent MRI to determine the presence of syringomyelia. Mean age at surgery was 12.5 years. Abnormal SAR was defined as unilateral or bilateral absence or hyporeflexia of SAR. We calculated indices of diagnostic utility of abnormal SAR for non-idiopathic scoliosis and for syringomyelia. Abnormal SAR, left thoracic curve pattern, gender, and curve flexibility were compared between scoliosis with syringomyelia and idiopathic scoliosis. Logistic regression analysis was performed with the existence of syringomyelia as the dependent variable and curve flexibility as the independent variable.</p> <p>Results</p> <p>Abnormal SAR was observed in 20 patients (prevalence 22%). All 6 patients with myopathic scoliosis displayed bilateral absence of SAR. The sensitivity of abnormal SAR for non-idiopathic scoliosis was 38%, with 96% specificity, 90% PPV (positive predictive value), and 60% NPV (negative predictive value). Syringomyelia was identified in 9 of the 93 patients (9.7%); 8 of these had abnormal SAR. The sensitivity of abnormal SAR for syringomyelia in presumed idiopathic scoliosis was 89%, with 95% specificity, 80% PPV, and 98% NPV. Gender, abnormal neurological findings, and curve flexibility differed significantly between patients with syringomyelia and those with idiopathic scoliosis (P < 0.05). In the logistic regression model, the area under the receiver operating characteristic (ROC) curve was 0.79 and the cut-off value of curve flexibility for syringomyelia was 50% (P = 0.08).</p> <p>Conclusion</p> <p>Abnormal SAR was a useful indicator not only for syringomyelia, but also for myogenic scoliosis.</p

A Cell Permeable Peptide Inhibitor of NFAT Inhibits Macrophage Cytokine Expression and Ameliorates Experimental Colitis

Nuclear factor of activated T cells (NFAT) plays a critical role in the development and function of immune and non-immune cells. Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we further investigate NFAT function in murine macrophages and determined the effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-γ induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10−/−) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was administered systemically to Il10−/− mice with piroxicam-induced colitis. 11R-VIVIT treated mice demonstrated significant improvement in colitis compared to mice treated with an inactive peptide. Moreover, decreased spontaneous secretion of IL-12 p40 and TNF in supernatants from colon explant cultures was demonstrated. In summary, NFAT, widely recognized for its role in T cell biology, also regulates important innate inflammatory pathways in macrophages. Selective blocking of NFAT via a cell permeable inhibitory peptide is a promising therapeutic strategy for the treatment of inflammatory bowel diseases

Haloperidol differentially modulates prepulse inhibition and p50 suppression in healthy humans stratified for low and high gating levels

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance

In vitro and in vivo mRNA delivery using lipid-enveloped pHresponsive polymer nanoparticles

Biodegradable core−shell structured nanoparticles with a poly(β-amino ester) (PBAE) core enveloped by a phospholipid bilayer shell were developed for in vivo mRNA delivery with a view toward delivery of mRNA-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. Messenger RNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of 30%. Particles loaded with mRNA administered intranasally (i.n.) in mice led to the expression of the reporter protein luciferase in vivo as soon as 6 h after administration, a time point when naked mRNA given i.n. showed no expression. At later time points, luciferase expression was detected in naked mRNA-treated mice, but this group showed a wide variation in levels of transfection, compared to particle-treated mice. This system may thus be promising for noninvasive delivery of mRNA-based vaccines.United States. Dept. of Defense (Institute for Soldier Nanotechnology, contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and HarvardSingapore. Agency for Science, Technology and ResearchHoward Hughes Medical Institute (Investigator