Novel ROSA26 Cre-reporter Knock-in C57BL/6N Mice Exhibiting Green Emission before and Red Emission after Cre-mediated Recombination

The Cre/loxP system is a strategy for controlling temporal and/or spatial gene expression through genome alteration in mice. As successful Cre/loxP genome alteration depends on Cre-driver mice, Cre-reporter mice are essential for validation of Cre gene expression in vivo. In most Cre-reporter mouse strains, although the presence of reporter product indicates the expression of Cre recombinase, it has remained unclear whether a lack of reporter signal indicates either no Cre recombinase expression or insufficient reporter gene promoter activity. We produced a novel ROSA26 knock-in Cre-reporter C57BL/6N strain exhibiting green emission before and red after Cre-mediated recombination, designated as strain R26GRR. Ubiquitous green fluorescence and no red fluorescence were observed in R26GRR mice. To investigate the activation of tdsRed, EGFP-excised R26GRR, R26RR, mice were produced through the crossing of C57BL/6N mice with R26GRR/Ayu1-Cre F₁ mice. R26RR mice showed extraordinarily strong red fluorescence in almost all tissues examined, suggesting ubiquitous activation of the second reporter in all tissues after Cre/loxP recombination. Moreover, endothelial cell lineage and pancreatic islet-specific expression of red fluorescence were detected in R26GRR/Tie2-Cre F₁ mice and R26GRR /Ins1-Cre F₁ mice, respectively. These results indicated that R26GRR mice are a useful novel Cre-reporter mouse strain. In addition, R26GRR mice with a pure C57BL/6N background represent a valuable source of green-to-red photoconvertible cells following Cre/loxP recombination for application in transplantation studies. The R26GRR mouse strain will be available from RIKEN BioResource Center (http://www.brc.riken.jp/lab/animal/en/).     

Coupling among growth rate response, metabolic cycle, and cell division cycle in yeast

We studied the steady-state responses to changes in growth rate of yeast when ethanol is the sole source of carbon and energy. Analysis of these data, together with data from studies where glucose was the carbon source, allowed us to distinguish a "universal" growth rate response (GRR) common to all media studied from a GRR specific to the carbon source. Genes with positive universal GRR include ribosomal, translation, and mitochondrial genes, and those with negative GRR include autophagy, vacuolar, and stress response genes. The carbon source-specific GRR genes control mitochondrial function, peroxisomes, and synthesis of vitamins and cofactors, suggesting this response may reflect the intensity of oxidative metabolism. All genes with universal GRR, which comprise 25% of the genome, are expressed periodically in the yeast metabolic cycle (YMC). We propose that the universal GRR may be accounted for by changes in the relative durations of the YMC phases. This idea is supported by oxygen consumption data from metabolically synchronized cultures with doubling times ranging from 5 to 14 h. We found that the high oxygen consumption phase of the YMC can coincide exactly with the S phase of the cell division cycle, suggesting that oxidative metabolism and DNA replication are not incompatible.     

The activity of a subterranean small mammal alters Afroalpine vegetation patterns and is positively affected by livestock grazing

Subterranean rodents can act as ecosystem engineers by shaping the landscape due to soil perturbation and herbivory. At the same time, their burrow density is affected by environmental conditions, vegetation and anthropogenic factors. Disentangling this complex interplay between subterranean rodents and their environment remains challenging. In our study, we analysed the interplay of abiotic conditions, vegetation patterns and human land-use and the burrow density of the giant root-rat (GRR; Tachyoryctes macrocephalus), a subterranean rodent endemic to the Afroalpine ecosystem of the Bale Mountains in south-east Ethiopia. Specifically, we examined the effects of GRR on plant species richness and vegetation cover and vice-versa, and how these reciprocal effects might be modulated by temperature, habitat wetness and grazing. Our results showed that increasing GRR burrow density led to decreased vegetation cover, and that effects of GRR on vegetation cover were slightly stronger than vice-versa. Considering the reciprocal causation models, we found that increasing plant species richness led to increased GRR burrow density, while GRR burrow density decreased as vegetation cover increased. Increases in habitat wetness and livestock grazing intensity also directly led to increased GRR burrow density. Our results stress the importance of subterranean ecosystem engineers on vegetation and highlight the vulnerability of these complex interactions to human activity.     

The GRR1 gene of Candida albicans is involved in the negative control of pseudohyphal morphogenesis

The opportunistic fungal pathogen Candida albicans can grow as yeast, pseudohyphae or true hyphae. C. albicans can switch between these morphologies in response to various environmental stimuli and this ability to switch is thought to be an important virulence trait. In Saccharomyces cerevisiae, the Grr1 protein is the substrate recognition component of an SCF ubiquitin ligase that regulates cell cycle progression, cell polarity and nutrient signaling. In this study, we have characterized the GRR1 gene of C. albicans. Deletion of GRR1 from the C. albicans genome results in a highly filamentous, pseudohyphal morphology under conditions that normally promote the yeast form of growth. Under hypha-inducing conditions, most cells lacking GRR1 retain a pseudohyphal morphology, but some cells appear to switch to hyphal-like growth and express the hypha-specific genes HWP1 and ECE1. The C. albicans GRR1 gene also complements the elongated cell morphology phenotype of an S. cerevisiae grr1Delta mutant, indicating that C. albicans GRR1 encodes a true orthologue of S. cerevisaie Grr1. These results support the hypothesis that the Grr1 protein of C. albicans, presumably as the F-box subunit of an SCF ubiquitin ligase, has an essential role in preventing the switch from the yeast cell morphology to a pseudohyphal morphology.     

Life tables and development of Bemisia argentifolii (Homoptera: Aleyrodidae) at different temperatures

The life history of Bemisia argentifolii Bellows & Perring (Homoptera: Aleyrodidae) on tomato (Lycopersicum spp.) was studied based on the age-stage, two-sex life table at 15, 20, 25, 28, 30, and 35 degrees C. The intrinsic rate of increase (r) at these temperatures is -0.0176, 0.0667, 0.1469, 0.1611, 0.1745, and 0.0989 d(-1), respectively. The relationship among the gross reproductive rate (GRR), the net reproductive rate (R0), and the preadult survivorship (l(a)) is consistent with GRR > l(a) x GRR > R0 for all results at different temperatures. The mean generation time is 81.9, 48.6, 28.4, 25.3, 22.1, and 18.2 d, respectively. The developmental rate of the egg stage at different temperatures fit a linear equation with a thermal summation 89.2 degree-days and a developmental threshold of 11.4 degrees C. The developmental rates of the nymphal stage fit the model of Stinner et al. and the parameters of C, Rmax, k1 and k2 were 0.085, 0.0833, 5.298, and -0.263, respectively.     

General Regression and Representation Model for Classification

Recently, the regularized coding-based classification methods (e.g. SRC and CRC) show a great potential for pattern classification. However, most existing coding methods assume that the representation residuals are uncorrelated. In real-world applications, this assumption does not hold. In this paper, we take account of the correlations of the representation residuals and develop a general regression and representation model (GRR) for classification. GRR not only has advantages of CRC, but also takes full use of the prior information (e.g. the correlations between representation residuals and representation coefficients) and the specific information (weight matrix of image pixels) to enhance the classification performance. GRR uses the generalized Tikhonov regularization and K Nearest Neighbors to learn the prior information from the training data. Meanwhile, the specific information is obtained by using an iterative algorithm to update the feature (or image pixel) weights of the test sample. With the proposed model as a platform, we design two classifiers: basic general regression and representation classifier (B-GRR) and robust general regression and representation classifier (R-GRR). The experimental results demonstrate the performance advantages of proposed methods over state-of-the-art algorithms.     

Altered Regulatory Responses to Glucose Are Associated with a Glucose Transport Defect in Grr1 Mutants of Saccharomyces Cerevisiae

The GRR1 gene of Saccharomyces cerevisiae affects glucose repression, cell morphology, divalent cation transport and other processes. We present a kinetic analysis showing that the grr1 mutant is also defective in high affinity glucose transport. In combination with a mutation in SNF3, a member of the glucose transporter gene family, grr1 strikingly impairs growth on glucose. These findings suggest that GRR1 and SNF3 affect glucose transport by distinct pathways. The mutation rgt1-1, a suppressor of snf3, restores both glucose transport and glucose repression to a grr1 mutant, but does not remedy the morphological defect. We suggest that GRR1 affects the glucose sensing process and that the association between transport and regulation may reflect the involvement of a transporter in glucose sensing.     

白术配伍人参前后挥发油调控慢性萎缩性胃炎大鼠AQP 3、4表达的比较研究

为探究参术药对配伍治疗慢性萎缩性胃炎的增效机制,本文就白术配伍人参前后挥发油成分物质基础变化及对慢性萎缩性胃炎大鼠胃组织水通道蛋白3(AQP 3)、水通道蛋白4(AQP 4)的影响进行了比较研究。采用水蒸气蒸馏法提取人参白术配伍前后挥发油,以GC-MS法表征挥发油化学特征,并随机将大鼠分成空白组、模型组、白术挥发油组及配伍挥发油组,使用MNNG建立慢性萎缩性胃炎模型,给药后观察各组胃黏膜组织显微、超微结构变化以及AQP 3、AQP 4的表达。结果显示,白术配伍人参后挥发油的提取量升高,经GC-MS测定,配伍后苍术酮相对含量降低,新增少量人参挥发油成分。显微及超微观察显示,模型组大鼠胃组织黏膜折叠皱起,黏膜层和固有层腺体萎缩严重,胃小凹形态改变,上皮细胞破损,炎症细胞大面积浸润,且病理评分明显高于正常组(P<0.05);各药物组与模型组相比,均缓解或改善上述病理结果,且配伍挥发油组表现更优。免疫组化结果显示,模型组大鼠胃黏膜AQP 3、AQP 4表达明显低于空白组(P<0.05);相较模型组,各药物组对胃黏膜AQP 3、AQP 4蛋白的表达有增加趋势或明显增加,且配伍挥发油组...     

Biochemical symptoms of hypothyreosis in the population of Warsaw region

Doctors in Warsaw region claimed that the results of fT4 and TSH examinations originating from different laboratories are incomparable. Therefore the Gaussian Reference Ranges (GRR) of archival sets of data from 6 laboratories (together 18793 fT4 and 44851 TSH results) were calculated separately with JEG method. The upper and lover ranges were compared with data from 11 bibliographical sources. It was found that in the investigated population the both averaged ranges (high and low) of GRR of fT4 are statistical significant lover then the reference data. In the same time the averaged upper range of GRR of TSH was higher than the averaged data from the literature. Based on statistic analysis of these results it could be estimated that about 20% of the investigated population show evident and about 50% show moderate signs of hypothyreosis.     

Implications of multilocus inheritance for gene-disease association studies

The impact of multilocus inheritance on the power of candidate gene association studies and the parameters derived therefrom is considered. Both case-control and family-based control designs are included. When the background heritability H (i.e., residual correlation) among sibs for the disease in question is high, the power of multiplex affected sibships versus singletons is diminished compared with the situation when background heritability is low. Thus, multiplex families for association studies are most advantageous for low heritability disorders. Estimates of genotype relative risk (GRR) are also distorted in multiplex sibships compared with singletons based on background heritability. In a case-control study, GRR is inflated in multiplex families, with the degree of inflation decreasing with background heritability. By contrast, in a TDT (parental control) study, GRR is deflated in multiplex families, with the degree of deflation increasing with background heritability (and no deflation when H is 0). Considering identical twins, the difference in genotype frequencies between concordant versus discordant MZ twin pairs for the candidate gene is large when the heritability is low, but modest when the heritability is high.     

Wildlife water utilization and importance of artificial waterholes during dry season at Ruaha National Park, Tanzania

Provision of water to wildlife is crucial during dry season along the Great Ruaha River (GRR) in Ruaha National Park due to mismanagement of water resources upstream. This paper shows that wildlife in the dry areas of the park utilizes effectively the water from natural and artificial waterholes dug in the sandy riverbed of the GRR. Artificial water holes help alleviate the effects of artificial water shortage in the river, and because the location of the artificial water holes varies annually, the impact on the vegetation of aggregating herbivores around water holes was minimized. Water quality was comparable in natural and artificial water holes, and was the highest in holes dug by elephants in the sandy river bed.     

The Nuclear Receptor Resource Project.

We have expanded the original Glucocorticoid Receptor Resource (GRR) database to include several individual resources as part of a larger project called the Nuclear Receptor Resource (NRR). In addition to the GRR, the NRR currently features the Thyroid Hormone Receptor Resource, the Androgen Receptor Resource, the Mineralocorticoid Receptor Resource, the Vitamin D Receptor Resource, and the Steroid Receptor Associated Proteins Resource. The goal of the NRR project is to provide a comprehensive resource for information on the nuclear receptor superfamily, and to provide a forum for the dissemination and discussion of both published and unpublished material on these proteins. Although the individual resources are managed from different servers, all the files are integrated and can be accessed through the project's Home Page, housed at http://nrr. georgetown.edu/nrr.html. In the near future, we hope to expand the project to contain information on other nuclear receptors and to better our electronic publication system. To accomplish this, we encourage the involvement of nuclear receptor investigators in the NRR.     

Life tables of Venturia canescens (Hymenoptera: Ichneumonidae) parasitizing the Mediterranean flour moth (Lepidoptera: Pyralidae)

Effects of temperature, adult feeding, and host instar on life table parameters of Venturia canescens Gravenhorst (Hymenoptera: Ichneumonidae) parasitizing larvae of Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) were studied in the laboratory. Experimental adults lived under various regimes of temperature (15, 20, 25, and 30 degrees C), food supply (with or without access to honey), and host instar (second, third, fourth, and fifth). Temperature increase resulted in higher values of the intrinsic rate of natural increase (r(m)), the net reproductive rate (R(o)), the finite capacity of increase (lambda), and the gross reproductive rate (GRR), whereas it was followed by decrease of the mean generation time (G) and the doubling time (DT) values. Feeding on honey caused remarkable increase of r(m), R(o), and GRR, whereas r(m) and lambda reached their maximum when full-grown hosts (fifth instar) were parasitized. This is the first time life table parameters of V. canescens have been studied. The findings of the current study are discussed on the basis of improving V. canescens performance as a biological agent against moth pests of stored products.     

The 20S proteasome processes NF-kappaB1 p105 into p50 in a translation-independent manner

The NF-kappaB p50 is the N-terminal processed product of the precursor, p105. It has been suggested that p50 is generated not from full-length p105 but cotranslationally from incompletely synthesized molecules by the proteasome. We show that the 20S proteasome endoproteolytically cleaves the fully synthesized p105 and selectively degrades the C-terminus of p105, leading to p50 generation in a ubiquitin-independent manner. As small as 25 residues C-terminus to the site of processing are sufficient to promote processing in vivo. However, any p105 mutant that lacks complete ankyrin repeat domain (ARD) is processed aberrantly, suggesting that native processing must occur from a precursor, which extends beyond the ARD. Remarkably, the mutant p105 that lacks the internal region including the glycine-rich region (GRR) is completely degraded by 20S proteasome in vitro. This suggests that the GRR impedes the complete degradation of the p105 precursor, thus contributing to p50 generation.