Effect of SNPs on Creatine Kinase Structure and Function: Identifying Potential Molecular Mechanisms for Possible Creatine Kinase Deficiency Diseases

Single-nucleotide polymorphisms (SNPs) are common genetic material changes that often occur naturally. SNPs can cause amino acid replacements that may lead to severe diseases, such as the well-known sickle-cell anemia. We constructed eight SNP mutants of human brain-type creatine kinase (CKB) based on bioinformatics predictions. The biochemical and biophysical characteristics of these SNP mutants were determined and compared to those of the wild-type creatine kinase to explore the potential molecular mechanisms of possible creatine kinase SNP-induced diseases. While the reactivation of six SNP mutants after heat shock dropped more than 45%, only three of them showed notable increases in ANS fluorescence intensity and decreases in catalytic efficiency. Among them, H26Y and P36T bind substrates as well as the wild-type form does, but the melting temperatures (T_m) dropped below body temperature, while the T59I mutant exhibited decreased catalytic activity that was most likely due to the much reduced binding affinity of this mutant for substrates. These findings indicate that SNPs such as H26Y, P36T and T59I have the potential to induce genetic diseases by different mechanisms.     

Drug discovery prospect from untapped species: indications from approved natural product drugs

Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery.     

Mammalian PIK3C3/VPS34: the key to autophagic processing in liver and heart

PIK3C3/Vps34 is the class III PtdIns3K that is evolutionarily conserved from yeast to mammals. Its central role in mammalian autophagy has been suggested through the use of pharmacological inhibitors and the study of its binding partners. However, the precise role of PIK3C3 in mammals is not clear. Using mouse strains that allow tissue-specific deletion of PIK3C3, we have described an essential role of PIK3C3 in regulating autophagy, and liver and heart function.     

Clue to a New Deafness Gene: A Large Chinese Nonsyndromic Hearing Loss Family Linked to DFNA4

Hereditary hearing loss is one of the most common neurosensory defects in humans.Approximately 70％ of cases are nonsyndromic and could be inherited in autosomal dominant,autosomal recessive,mitochondrial,X-linked,and Y-linked manners (Wang et al.,2004;Alford,2011).The autosomal dominant type,comprising 15％-20％ of nonsyndromic hearing loss,is monogenic and genetically heterogeneous.Since the first dominant deafness locus (DFNA1) was identified in 1992,a total of 64 DFNA loci have been mapped (DFNA1-DFNA64),and 27 corresponding genes have been identified (http://hereditaryhearingloss.org).Previous studies have revealed that one deafness locus can be linked to more than one gene (Bayazit and Yilmaz,2006),and the question "one locus,how many genes?" was first raised about a decade ago (Van-Hauwe et al.,1999).So far,several loci,including DFNA2 and DFNA3,have been shown to be related to one or more genes,showing high genetic heterogeneity in hereditary hearing loss (Grifa et al.,1999;Goldstein and Lalwani,2002;Yan et al.,2011).     

黑龙江4种铁线莲色谱指纹特征比较分析

运用化学计量学方法,比较分析黑龙江4种铁线莲植物,辣蓼铁线莲、棉团铁线莲、褐毛铁线莲、齿叶铁线莲根及根茎石油醚提取物的色谱指纹特征。色谱-光谱数据的多元分辨结果表明4种铁线莲的色谱指纹特征中,总计至少有45种化学成分存在,共有的化学成分为14种,单独的化学成分分别为3、6、2及2种。聚类分析显示,辣蓼铁线莲与棉团铁线莲间的相似程度在4种铁线莲全部两-两组合的相似程度中最小。     

Development of an enrichment culture growing at low temperature used for ensiling rice straw

To speed up the conversion of rice straw into feeds in a low-temperature region, a start culture used for ensiling rice straw at low temperature was selected by continuous enrichment cultivation. During the selection, the microbial source for enrichment was rice straw and soil from two places in Northeast China. Lab-scale rice straw fermentation at 10 degrees C verified, compared with the commercial inocculant, that the selected start culture lowered the pH of the fermented rice straw more rapidly and produced more lactic acid. The results from denatured gradient gel eletrophoresis showed that the selected start culture could colonize into the rice straw fermentation system. To analyze the composition of the culture, a 16S clone library was constructed. Sequencing results showed that the culture mainly consisted of two bacterial species. One (A) belonged to Lactobacillus and another (B) belonged to Leuconostoc. To make clear the roles of composition microbes in the fermented system, quantitative PCR was used. For species A, the DNA mass increased continuously until sixteen days of the fermentation, which occupied 65%. For species B, the DNA mass amounted to 5.5% at six days of the fermentation, which was the maximum relative value during the fermentation. To the authors' best knowledge, this is the first report on ensiling rice straw with a selected starter at low temperature and investigation of the fermented characteristics.     

Arsenic upregulates MMP-9 and inhibits wound repair in human airway epithelial cells

As part of the innate immune defense, the polarized conducting lung epithelium acts as a barrier to keep particulates carried in respiration from underlying tissue. Arsenic is a metalloid toxicant that can affect the lung via inhalation or ingestion. We have recently shown that chronic exposure of mice or humans to arsenic (10-50 ppb) in drinking water alters bronchiolar lavage or sputum proteins consistent with reduced epithelial cell migration and wound repair in the airway. In this report, we used an in vitro model to examine effects of acute exposure of arsenic (15-290 ppb) on conducting airway lung epithelium. We found that arsenic at concentrations as low as 30 ppb inhibits reformation of the epithelial monolayer following scrape wounds of monolayer cultures. In an effort to understand functional contributions to epithelial wound repair altered by arsenic, we showed that acute arsenic exposure increases activity and expression of matrix metalloproteinase (MMP)-9, an important protease in lung function. Furthermore, inhibition of MMP-9 in arsenic-treated cells improved wound repair. We propose that arsenic in the airway can alter the airway epithelial barrier by restricting proper wound repair in part through the upregulation of MMP-9 by lung epithelial cells.     

Dynamic modeling for shear stress induced ATP release from vascular endothelial cells

A dynamic model is proposed for shear stress induced adenosine triphosphate (ATP) release from endothelial cells (ECs). The dynamic behavior of the ATP/ADP concentration at the endothelial surface by viscous shear flow is investigated through simulation studies based on the dynamic ATP release model. The numerical results demonstrate that the ATP/ADP concentration against time at endothelium-fluid interface predicted by the dynamic ATP release model is more consistent with the experimental observations than that predicted by previous static ATP release model.     

Spatial distribution of Holcocerus hippophaecolus (Lepidoptera: Cossidae) pupae in a seabuckthorn (Hippophae rhamnoides) stand

The seabuckthorn carpenter moth, Holcocerus hippophaecolus, which has a generation time of four years, is recently becoming one of the major pests of the seabuckthorn (Hippophae rhamnoides) in Inner Mongolia, Liaoning, Shanxi, Ningxia and Shaanxi of China (Hua et al., 1990). The larvae of the H. hippophaecolus mainly damage the stems and roots of the seabuckthorn, and the mature larvae pupate in the soil. The spatial distribution of the pupae was analyzed by using biostatistics and geostatistics in order to effectively control the insect and further study the spatial distribution of the population. Results show that most of the pupae (90%) had an eclosion time span from early June to the end of July. The sex ratio of the pupae was nearly 1:1 in the woodland samples. In addition, 24.3% of the 971 trees investigated had pupae and it ranged from 0 to 4 per tree within a distance of 1.3 m from the base of the stem. 90% of the pupae were aggregated within a distance of 1 m from the base of the stem. The pupae show intense spatial aggregation in the sampled woodland which had an 11.1 m spatial dependence and a 90.7% intensity in the local spatial continuity. Moreover, the population presented an intensive spotted distribution and many aggregated spots were found in the woodlands. As for the relationship between grid size and variogram of the pupae, the variations in the range, the intensity of local spatial continuity and the sill were all very low or non-existent when the grid size was 5 m, 6 m or 7 m. Whereas, the value of the decisive coefficient was the biggest when the grid size was 5 m making it the ideal grid size.