Naturally Occurring Mutations Alter the Stability of Polycystin-1 Polycystic Kidney Disease (PKD) Domains

Mutations in polycystin-1 (PC1) can cause autosomal dominant polycystic kidney disease, which is a leading cause of renal failure. The available evidence suggests that PC1 acts as a mechanosensor, receiving signals from the primary cilia, neighboring cells, and extracellular matrix. PC1 is a large membrane protein that has a long N-terminal extracellular region (about 3000 amino acids) with a multimodular structure including 16 Ig-like polycystic kidney disease (PKD) domains, which are targeted by many naturally occurring missense mutations. Nothing is known about the effects of these mutations on the biophysical properties of PKD domains. Here we investigate the effects of several naturally occurring mutations on the mechanical stability of the first PKD domain of human PC1 (HuPKDd1). We found that several missense mutations alter the mechanical unfolding pathways of HuPKDd1, resulting in distinct mechanical phenotypes. Moreover, we found that these mutations also alter the thermodynamic stability of a structurally homologous archaeal PKD domain. Based on these findings, we hypothesize that missense mutations may cause autosomal dominant polycystic kidney disease by altering the stability of the PC1 ectodomain, thereby perturbing its ability to sense mechanical signals.     

Low-dose ionizing radiation effects on differentiation of HL-60 cells

The biological effects of low-dose radiation have attracted attention, but data are currently insufficient to fully understand the beneficial role of the phenomenon. In the present study, we have investigated the effects of low doses of gamma-irradiation alone and in combination with all-trans-retinoic acid (RA) on proliferation, apoptosis and differentiation of the human promyelocytic leukemia HL-60 cells. Changes in cell behavior and protein expression were determined with the use of light and fluorescent microscopy, immunocytochemical and Western blot analysis. Low-dose irradiation with 1–100 cGy caused a dose-dependent inhibition of HL-60 cell proliferation, and induced apoptosis and differentiation to granulocytes with an increase in the number of CD15-positive cells. Pre-irradiation with 1–100 cGy for 24 h before treatment with RA promoted apoptosis but did not impair RA-induced differentiation. Both processes were associated with a decrease in the expression of the proliferating cell nuclear antigen (PCNA), BCL-2, c-MYC, and changes in both cytosolic and nuclear levels of protein tyrosine-phosphorylation as well as protein kinase C alpha or beta isoforms. These results demonstrate the beneficial role of low-dose irradiation in modulating leukemia cell proliferation, differentiation and apoptosis.     

Fine mapping and candidate gene analysis of dense and erect panicle 3, DEP3, which confers high grain yield in rice (Oryza sativa L.)

Architecture of the rice inflorescence, which is determined mainly by the morphology, number and length of primary and secondary inflorescence branches, is an important agronomical trait. In the current study, we characterized a novel dense and erect panicle (EP) mutant, dep3, derived from the Oryza sativa ssp. japonica cultivar Hwacheong treated with N-methyl-N-nitrosourea. The panicle of the dep3 mutant remained erect from flowering to full maturation, whereas the panicle of the wild type plant began to droop after flowering. The dep3 mutation also regulated other panicle characteristics, including panicle length, grain shape and grain number per panicle. Anatomical observations revealed that the dep3 mutant had more small vascular bundles and a thicker culm than wild type plants, explaining the EP phenotype. Genetic analysis indicated that the phenotype with the dense and EP was controlled by a single recessive gene, termed dep3. The DEP3 gene was identified as the candidate via a map-based cloning approach and was predicted to encode a patatin-like phospholipase A2 (PLA2) superfamily domain-containing protein. The mutant allele gene carried a 408?bp genomic deletion within LOC_Os06g46350, which included the last 47?bp coding region of the third exon and the first 361?bp of the 3??-untranslated region. Taken together, our results indicated that the patatin-like PLA2 might play a significant role in the formation of vascular bundles, and that the dep3 mutant may provide another EP resource for rice breeding programs.     

Depth of edge influence of the agricultural-forest landscape boundary,Southwestern China

The landscape boundary is an important component of a landscape and often plays an indispensable role in regulating ecological flows. The primary objective of this study was to estimate how far the edge effects on agricultural-forest landscape boundaries can penetrate into the forest and agricultural field. This will serve as a basis for understanding the interaction between forest and agricultural fields in the mountainous area of southwestern China and provide scientific basis for the practice of the policy of “returning agricultural field to forest.” Based on field investigations, three types of boundaries with six sampling transects were selected. We investigated the soil moisture, soil nutrients and vegetation diversity along the transect gradient and explored the depth of edge influence (DEI) with moving split-window techniques for analyzing the data. DEI for soil moisture changed with the seasons, ranging from 6 m in the pepper field to 2 m in the forest during the dry season, and from 12 m in the pepper field to 2 m in the forest after heavy rain. DEI based on soil organic matter ranged from 1.5 to 10 m in the forest field, while it was not detected based on other soil nutrient factors. DEI based on vegetation diversity varied from 4 to 26 m and from 10 to 31 m in the forest and agricultural fields, respectively. These results provide the scientific basis for the policy “returning agricultural field to forest”. Based on these field observations, reducing human disturbance and revegetating with natural shrubs and meadows could be more effective for vegetation conservation in terms of soil moisture and soil nutrient content in the arid valley of the Minjiang River.     

Comparison of three ELISA kits for the differentiation of foot-and-mouth disease virus-infected from vaccinated animals

A study was performed to validate 3 FMDV 3ABC-I-ELISA kits developed in China for the differentiation of FMDV infected and vaccinated animals. Sets of sera from naive and vaccinated cattle as well as from cattle that had been infected were tested for antibodies against nonstructural proteins (NSPs) of FMDV by commercial diagnosis kits, Ceditest® FMDV-NS (Ceditest® kit), UBI® FMDV NONSTRUCTURAL PROTEIN ELISA DIRECTION INSERT (UBI® kit) and a FMDV 3ABC-I-ELISA kit developed at the Lanzhou Veterinary Research Institute. The test parameters (sensitivity and specificity) of the three kits were determined, and the result obtained from FMD 3ABC-I-ELISA kit was compared with that obtained from two foreign kits. The results indicated that the coincidence rate between the FMDV 3ABC-I-ELISA and Ceditest® kits was 98.05%, and the coincidence rate between the FMDV 3ABC-I-ELISA and UBI® kits was 94.4%; the sensitivity of both Ceditest® and FMDV 3ABC-I-ELISA kit was 100%. However, the sensitivity of the UBI® kit was only 81.8%. With sera from naive or vaccinated non-infected animals, the specificity of all tests exceeded 90%.     

Developmental expression of the receptor for advanced glycation end-products (RAGE) and its response to hyperoxia in the neonatal rat lung

Background  

The receptor for advanced glycation end products (mRAGE) is associated with pathology in most tissues, while its soluble form (sRAGE) acts as a decoy receptor. The adult lung is unique in that it expresses high amounts of RAGE under normal conditions while other tissues express low amounts normally and up-regulate RAGE during pathologic processes. We sought to determine the regulation of the soluble and membrane isoforms of RAGE in the developing lung, and its expression under hyperoxic conditions in the neonatal lung.     

Properties,Microstructure and Heat Seal Ability of Bilayer Films Based on Fish Gelatin and Emulsified Gelatin Films

Bilayer films prepared by the lamination of fish gelatin film (GF) and its corresponding emulsified film (EF) with different thickness ratios (7:3, 5:5 and 3:7) were characterized. Bilayer films had the similar tensile strength (TS) to EF (p > 0.05) but showed lower elongation at break (EAB) (p < 0.05). All bilayer films showed the lower water vapor permeability (WVP) but higher oxygen permeability (OP) than GF. Bilayer films had varying ΔE* (total color different), where the highest value was observed in that laminated with higher thickness ratio of EF (p < 0.05). Lower light transmission and higher transparency value were obtained for bilayer films, compared to GF (p < 0.05). Based on scanning electron microscopic (SEM) cross-section micrographs, all bilayer films consisted of two layers. Differential scanning calorimetric (DSC) analysis revealed that the bilayer films had the higher glass transition temperature (T _g) than GF but lower than EF. All bilayer films were heat sealable, however their seal strength and seal efficiency were lower than those of GF (p < 0.05). Therefore, the thickness ratios of GF and EF had a marked effect on the mechanical and barrier properties as well as heat sealing ability of resulting bilayer films.     

Effect of organosolv pretreatment on mechanically pretreated biomass by use of concentrated ethanol as the solvent

In this study, we determined the effect of organosolv pretreatment on herbaceous biomasses corn stover and wheat straw, by using high-concentration ethanol as the solvent. A high-concentration of ethanol allows for the easy reuse and recycling of the solvent. First, we tested the effects of ethanol pretreatments at 60 and 99.5% (w/w) and found that highest solvent concentration resulted in low glucose digestibility. The maximum enzymatic glucose digestibility with 60% ethanol was 92.6% at 190°C for 120 min (using corn stover) and 86.9% at 190°C for 120 min (using wheat straw). In contrast, the digestion rates with 99.5% ethanol were 68.8 and 77.4% under the same conditions, respectively, indicating that there is a limit to the use of high-concentration ethanol as the solvent. To overcome this limitation, we applied a mechanical pretreatment step before the chemical pretreatment. Subsequently, glucose digestibility increased significantly to 93.1% with 99.5% ethanol as the solvent. Additionally the enzymatic digestibility of mechanically pretreated corn stover was higher than that of non-pretreated corn stover by about 40%. Taken together, these results confirm the efficacy of using high-concentration ethanol as a solvent for organosolv pretreatment when done in conjunction with mechanical pretreatment.     

Pictures,Preparations, and Living Processes: The Production of Immediate Visual Perception (<Emphasis Type="Italic">Anschauung</Emphasis>) in late-19th-Century Physiology

This paper addresses the visual culture of late-19th-century experimental physiology. Taking the case of Johann Nepomuk Czermak (1828–1873) as a key example, it argues that images played a crucial role in acquiring experimental physiological skills. Czermak, Emil Du Bois-Reymond (1818–1896) and other late-19th-century physiologists sought to present the achievements and perspective of their discipline by way of immediate visual perception (unmittelbare Anschauung). However, the images they produced and presented for this purpose were strongly mediated. By means of specifically designed instruments, such as the cardioscope, the contraction telegraph, and the frog pistol, and of specifically constructed rooms, so-called spectatoriums, physiologists trained and controlled the perception of their students before allowing them to conduct experiments on their own. Studying the material culture of physiological image production reveals that technological resources such as telegraphy, photography, and even railways contributed to making physiological facts anschaulich. At the same time, it shows that the more traditional image techniques of anatomy played an important role in physiological lecture halls, especially when it came to displaying the details of vivisection experiments to the public. Thus, the images of late 19th century physiology stood half-way between machines and organisms, between books and instruments.This paper was written in the context of ten project, The Experimentalizaiton of Life: Configurations of Life Sciences, Art, and Technology (1830–1930). The project is based at the Max Planck Institute for the History of Science (Dept. III: Hans-Jörg Rheinberger), Berlin, and receives funding from the Volkswagen Stiftung, Hannover. A first draft of this paper was presented, accompanied by Sven Dierig on the Virtual Laboratory, at the Institute of Theater Sciences, Free university Berlin, in December 2000. I would like to thank Sven Dierig and the other members of the project as well as Nick Hopwood, Skúli Sigurdsson and the anonymous referees and the editors of this journal for their helpful comments on an earlier version of this paper. Thanks also to Laurie McLaughlin and Nancy Anderson for helping me with the English version of the text.