Pigs as Models of Preclinical Studies and In Vivo Bioreactors for Generation of Human Organs

Pigs are valuable and essential large animal models for human medical applications, including for stem cell therapy. Moreover, substantial effort has been made to directly engraft genetically engineered pig organs in the human body and to use pigs as in vivo bioreactors for the growth and development of human cells, tissue, or organs. However, engraftment of human cells in pigs has not yet been achieved. Although severe combined immunodeficient pigs have been developed, which can accept human biological materials, these pigs do not have practical value at present owing to difficulty in their care. To overcome these current limitations, we have proposed the generation of operational immunodeficient pig models by simply removing the thymus and spleen, enabling the long-term accommodation of human tissue. In this review, we summarize research progress on xenotransplantation animal models that accept human cells, tissues, or organs

RNA interference of gonadotropin-inhibitory hormone gene induces arousal in songbirds.

Gonadotropin-inhibitory hormone (GnIH) was originally identified in quail as a hypothalamic neuropeptide inhibitor of pituitary gonadotropin synthesis and release. However, GnIH neuronal fibers do not only terminate in the median eminence to control anterior pituitary function but also extend widely in the brain, suggesting it has multiple roles in the regulation of behavior. To identify the role of GnIH neurons in the regulation of behavior, we investigated the effect of RNA interference (RNAi) of the GnIH gene on the behavior of white-crowned sparrows, a highly social songbird species. Administration of small interfering RNA against GnIH precursor mRNA into the third ventricle of male and female birds reduced resting time, spontaneous production of complex vocalizations, and stimulated brief agonistic vocalizations. GnIH RNAi further enhanced song production of short duration in male birds when they were challenged by playbacks of novel male songs. These behaviors resembled those of breeding birds during territorial defense. The overall results suggest that GnIH gene silencing induces arousal. In addition, the activities of male and female birds were negatively correlated with GnIH mRNA expression in the paraventricular nucleus. Density of GnIH neuronal fibers in the ventral tegmental area was decreased by GnIH RNAi treatment in female birds, and the number of gonadotropin-releasing hormone neurons that received close appositions of GnIH neuronal fiber terminals was negatively correlated with the activity of male birds. In summary, GnIH may decrease arousal level resulting in the inhibition of specific motivated behavior such as in reproductive contexts

Convex effective potential of O(N)O(N)-symmetric phi4phi^4 theory for large NN

We obtain effective potential of $O(N)$-symmetric $\phi^4$ theory for large $N$ starting with a finite lattice system and taking the thermodynamic limit with great care. In the thermodynamic limit, it is globally real-valued and convex in both the symmetric and the broken phases. In particular, it has a flat bottom in the broken phase. Taking the continuum limit, we discuss renormalization effects to the flat bottom and exhibit the effective potential of the continuum theory in three and four dimensions.On the other hand the effective potential is nonconvex in a finite lattice system. Our numerical study shows that the barrier height of the effective potential flattens as a linear size of the system becomes large. It decreases obeying power law and the exponent is about $-2$. The result is clearly understood from dominance of configurations with slowly-rotating field in one direction.Comment: New results on finite-size system are added. LaTeX, 21 pages, 6 figure

Factors affecting commencement and cessation of smoking behaviour in Malaysian adults

<p>Abstract</p> <p>Background</p> <p>Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as <it>bidi </it>and <it>rokok daun </it>are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs.</p> <p>Methods</p> <p>Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios.</p> <p>Results</p> <p>Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01).</p> <p>Conclusions</p> <p>Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation.</p

Scanning Three-Dimensional X-ray Diffraction Microscopy with a Spiral Slit

Recently, nondestructive evaluation of the stresses localized in grains was achieved for plastically deformed low-carbon steel using scanning three-dimensional X-ray diffraction (S3DXRD) microscopy with a conical slit. However, applicable metals and alloys were restricted to a single phase and evaluated stress was underestimated due to the fixed Bragg angles of the conical slit optimized to αFe. We herein propose S3DXRD with a rotating spiral slit adaptable to various metals and alloys and accurate stress evaluation with sweeping Bragg angles. Validation experiments with a 50-keV X-ray microbeam were conducted for low-carbon steel as a body-centered cubic (BCC) phase and pure Cu as a face-centered cubic (FCC) phase. As a result of orientation mapping, polygonal grain shapes and clear grain boundaries were observed for both BCC and FCC metals. Thus, it was demonstrated that S3DXRD with a rotating spiral slit will be applicable to various metals and alloys, multiphase alloys, and accurate stress evaluation using a X-ray microbeam with a higher photon energy within an energy range determined by X-ray focusing optics. In principle, this implies that S3DXRD becomes applicable to larger and thicker metal and alloy samples instead of current miniature test or wire-shaped samples if a higher-energy X-ray microbeam is available