ALBERT

Description: Background: Mn oxides occur in a wide variety of geological settings and exert considerable influences on the components and chemical behaviors of sediments and soils. Microbial reduction of Mn oxides is an important process found in many different environments including marine and freshwater sediments, lakes, anoxic basins, as well as oxic-anoxic transition zone of ocean. Although the pathway of Mn anaerobic reduction by two model bacteria, Geobacter and Shewanella, has been intensively studied, Mn bio-reduction is still the least well-explored process in nature. Particularly, reduction of Mn oxides by other bacteria and in the presence of O 2 has been fewly reported in recent publishes. Results: A series of experiments were conducted to understand the capability of Dietzia DQ12-45-1b in bioreduction of birnessite. In anaerobic systems, Mn reduction rate reached as high as 93% within 4 weeks when inoculated with 1.0 × 10 10 cells/mL Dietzia DQ12-45-1b strains. Addition of AQDS enhanced Mn reduction rate from 53 to 91%. The anaerobic reduction of Mn was not coupled by any increase in bacterial protein concentration, and the reduction rate in the stable stage of day 2–14 was found to be in good proportion to the protein concentration. The anaerobic reduction of birnessite released Mn(II) either into the medium or adsorbed on the mineral or bacteria surface and resulted in the dissolution of birnessite as indicated by XRD, SEM and XANES. Under aerobic condition, the reduction rate was only 37% with a cell concentration of 1.0 × 10 10 cells/mL, much lower than that in parallel anaerobic treatment. Bacterial growth under aerobic condition was indicated by time-course increase of protein and pH. In contrast to anaerobic experiments, addition of AQDS decreased Mn reduction rate from 25 to 6%. The reduced Mn(II) combined with carbon dioxide produced by acetate metabolism, as well as an alkaline pH environment given by cell growth, finally resulted in the formation of Mn(II)-bearing carbonate (kutnohorite), which was verified by XRD and XANES results. The system with the highest cell concentration of 1.0 × 10 10 cells/mL gave rise to the most amount of kutnohorite, while concentration of Mn(II) produced with cell concentration of 6.2 × 10 8 cells/mL was too low to thermodynamically favor the formation of kutnohorite but result in the formation of aragonite instead. Conclusion: Dietzia DQ12-45-1b was able to anaerobically and aerobically reduce birnessite. The rate and extent of Mn(IV) reduction depend on cell concentration, addition of AQDS or not, and presence of O 2 or not. Meanwhile, Mn(IV) bioreduction extent and suspension conditions determined the insoluble mineral products.

Description: Background: Revealing genetic mechanisms behind specific physiological characteristics of Saccharomyces cerevisiae from specific environments is important for industrial applications and requires precise understanding. Results: Maotai strain MT1 was isolated from the complicated Chinese Maotai-flavored liquor-making environment with extremely high temperatures, and acidic and ethanol stresses. Compared with the type strain S288c, MT1 can tolerate high acidity (pH 2.0), high ethanol levels (16 %) and high temperatures (44 °C). In addition, MT1 can simultaneously utilize various sugars, including glucose, sucrose, galactose, maltose, melibiose, trehalose, raffinose and turanose. Genomic comparisons identified a distinct MT1 genome, 0.5 Mb smaller than that of S288c. There are 145 MT1-specific genes that are not in S288c, including MEL1, MAL63, KHR1, BIO1 and BIO6. A transcriptional comparison indicated that HXT5 and HXT13, which are theoretically repressed by glucose, were no longer inhibited in MT1 and were highly expressed even in a medium containing 70 g/L glucose. Thus, other sugars may be co-utilized with glucose by MT1 without diauxic growth. Conclusions: Based on a functional genomics analysis, we revealed the genetic basis and evolutionary mechanisms underlying the traits of the Chinese Maotai-flavored yeast MT1. This work provides new insights for the genetic breeding of yeast and also enriches the genetic resources of yeast.

Description: Small-molecule compounds that inhibit human immunodeficiency virus type 1 (HIV-1) infection can be used not only as drug candidates, but also as reagents to dissect the life cycle of the virus. Thus, it is des...

Description: Background: Insulin receptor (InsR) and insulin signaling proteins are widely distributed throughout the kidney cortex. Insulin signaling can act in the kidney in multiple ways, some of which may be totally independent of its primary role of the maintenance of whole-body glucose homeostasis. However, descriptions of the insulin signaling in renal glomerular mesangial cells (MCs) are quite limited and the roles of insulin signaling in MC functions have not been sufficiently elucidated. Results: InsR silencing induced a unique phenotype of reduced fibronectin (FN) accumulation in renal glomerular MCs. Transcription level of FN was not significant changed in the InsR silenced cells, suggesting the phenotype switching was caused by post-transcriptional modification. The decreased expression of InsR was associated with enhanced activity of insulin-like growth factor-1 receptor (IGF-1R)/PI3K/Akt signaling pathway which contributed in part to the attenuation of cellular FN accumulation. Formation of IGF-1R homodimer was increased in the InsR silenced cells. The InsR silenced cells also showed increased sensitivity to exogenous IGF-1, and increased PI3K activity was reversed significantly by incubating cells with IGF-1R specific antagonist, AG538. PI3K/Akt dependent activation of cAMP response element-binding protein (CREB)-1 induced expression of matrix metalloproteinase (MMP)-9 and suppressing MMP activity by doxycycline partially reversed FN accumulation in the InsR silenced cells. Conclusions: The effects of InsR silencing on cellular FN accumulation in vitro are, at least partially, mediated by increased degradation of FN by MMPs which is induced by enhanced signaling sequence of IGF-1R/PI3K/Akt/CREB-1.

Description: Background: Small-molecule compounds that inhibit human immunodeficiency virus type 1 (HIV-1) infection can be used not only as drug candidates, but also as reagents to dissect the life cycle of the virus. Thus, it is desirable to have an arsenal of such compounds that inhibit HIV-1 infection by various mechanisms. Until now, only a few small-molecule compounds that inhibit nuclear entry of viral DNA have been documented. Results: We identified a novel, small-molecule compound, SJP-L-5, that inhibits HIV-1 infection. SJP-L-5 is a nitrogen-containing, biphenyl compound whose synthesis was based on the dibenzocyclooctadiene lignan gomisin M2, an anti-HIV bioactive compound isolated from Schisandra micrantha A. C. Smith. SJP-L-5 displayed relatively low cytotoxicity (50 % cytoxicity concentrations were greater than 200 μg/ml) and high antiviral activity against a variety of HIV strains (50 % effective concentrations (EC 50 )) of HIV-1 laboratory-adapted strains ranged from 0.16–0.97 μg/ml; EC 50 s of primary isolates ranged from 1.96–5.33 μg/ml). Analyses of the viral DNA synthesis indicated that SJP-L-5 specifically blocks the entry of the HIV-1 pre-integration complex (PIC) into the nucleus. Further results implicated that SJP-L-5 inhibits the disassembly of HIV-1 particulate capsid in the cytoplasm of the infected cells. Conclusions: SJP-L-5 is a novel small-molecule compound that inhibits HIV-1 nuclear entry by blocking the disassembly of the viral core.

Description: ObjectiveCigarette smoking had been confirmed as an increased risk for dyslipidemia, but none of the evidence was from long-lived population. In present study, we detected relationship between cigarette smoking habits and serum lipid/lipoprotein (serum Triglyceride (TG), Total cholesterol (TC), Low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) among Chinese Nonagenarians/Centenarian. Methods: The present study analyzed data from the survey that was conducted on all residents aged 90 years or more in a district, there were 2,311,709 inhabitants in 2005. Unpaired Student's t test, chi2 test, and multiple logistic regression were used to analyze datas. Results: The individuals included in the statistical analysis were 216 men and 445 women. Current smokers had lower level of TC (4.05 +/- 0.81 vs. 4.21 +/- 0.87, t = 2.403, P = 0.017) and lower prevalence of hypercholesteremia (9.62% vs. 15.13%, chi2 = 3.018,P = 0.049) than nonsmokers. Unadjusted and adjusted multiple logistic regressions showed that cigarette smoking was not associated with risk for abnormal serum lipid/lipoprotein. Conclusions: In summary, we found that among Chinese nonagenarians/centenarians, cigarette smoking habits were not associated with increased risk for dyslipidemia, which was different from the association of smoking habits with dyslipidemia in general population.

Description: Background: HER2 plays a critical role in the pathogenesis of many cancers and is linked to poor prognosis or cancer metastases. Monoclonal antibodies, such as Herceptin against HER2-overexpressing cancers, have showed satisfactory clinical therapeutic effect. However, they have difficulty to surmount obstacles to enter cells or blood-brain barrier. Results: In this study, a cell-penetrating peptide Arg9 was linked to the C-terminus of anti-HER2 single chain antibody (MIL5scFv). Flow cytometry, confocal microscopy and electron microscopy analysis all revealed that Arg9 peptide facilitated the penetration of MIL5scFv into HER2-negative cell line NIH3T3 and orientate in mitochondria. More interestingly, Western blot assay showed the potential enhanced bioactivity of MIL5scFv-Arg9 in HER2+ cell line SKOV3, indicating that Arg9 could help large molecules (e.g. antibody) to penetrate into cells and therefore enhance its anti-neoplastic function. Conclusions: Our work represented an attractive by preliminary strategy to enhance the therapeutic effect of existing antibodies by entering cells easier, or more desirable, surmounting the physical barriers, especially in hard-to-reach cancers such as brain metastases cases.

Description: Background: Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is known that thousands of isoforms bind themselves through specific homophilic interactions, a process which provides the basis for cellular self-recognition. Detailed biochemical studies of specific isoforms strongly suggest that homophilic binding, i.e. the formation of homodimers by identical Dscam1 isomers, is of great importance for the self-avoidance of neurons. Due to experimental limitations, it is currently impossible to measure the homophilic binding affinities for all 19,000 potential isoforms. Results: Here we reconstructed the DNA sequences of an ancestral Dscam form (which likely existed approximately 40?~?50 million years ago) using a comparative genomic approach. On the basis of this sequence, we established a working model to predict the self-binding affinities of all isoforms in both the current and the ancestral genome, using machine-learning methods. Detailed computational analysis was performed to compare the self-binding affinities of all isoforms present in these two genomes. Our results revealed that 1) isoforms containing newly derived variable domains exhibit higher self-binding affinities than those with conserved domains, and 2) current isoforms display higher self-binding affinities than their counterparts in the ancient genome. As thousands of Dscam isoforms are needed for the self-avoidance of the neuron, we propose that an increase in self-binding affinity provides the basis for the successful evolution of the arthropod brain. Conclusions: Our data presented here provide an excellent model for future experimental studies of the binding behavior of Dscam isoforms. The results of our analysis indicate that evolution favored the rise of novel variable domains thanks to their higher self-binding affinities, rather than selection merely on the basis of simple expansion of isoform diversity, as that this particular selection process would have established the powerful mechanisms required for neuronal self-avoidance. Thus, we reveal here a new molecular mechanism for the successful evolution of arthropod brains.

Description: Background: The pepper fruit is the second most consumed vegetable worldwide. However, low temperature affects the vegetative development and reproduction of the pepper, resulting in economic losses. To identify cold-related genes regulated by abscisic acid (ABA) in pepper seedlings, cDNA representational difference analysis was previously performed using a suppression subtractive hybridization method. One of the genes cloned from the subtraction was homologous to Solanum tuberosum MBF1 (StMBF1) encoding the coactivator multiprotein bridging factor 1. Here, we have characterized this StMBF1 homolog (named CaMBF1) from Capsicum annuum and investigated its role in abiotic stress tolerance. Results: Tissue expression profile analysis using quantitative RT-PCR showed that CaMBF1 was expressed in all tested tissues, and high-level expression was detected in the flowers and seeds. The expression of CaMBF1 in pepper seedlings was dramatically suppressed by exogenously supplied salicylic acid, high salt, osmotic and heavy metal stresses. Constitutive overexpression of CaMBF1 in Arabidopsis aggravated the visible symptoms of leaf damage and the electrolyte leakage of cell damage caused by cold stress in seedlings. Furthermore, the expression of RD29A, ERD15, KIN1, and RD22 in the transgenic plants was lower than that in the wild-type plants. On the other hand, seed germination, cotyledon greening and lateral root formation were more severely influenced by salt stress in transgenic lines compared with wild-type plants, indicating that CaMBF1-overexpressing Arabidopsis plants were hypersensitive to salt stress. Conclusions: Overexpression of CaMBF1 in Arabidopsis displayed reduced tolerance to cold and high salt stress during seed germination and post-germination stages. CaMBF1 transgenic Arabidopsis may reduce stress tolerance by downregulating stress-responsive genes to aggravate the leaf damage caused by cold stress. CaMBF1 may be useful for genetic engineering of novel pepper cultivars in the future.

Description: Background: Cis-natural antisense transcripts (cis-NATs) are RNAs transcribed from the antisense strand of a gene locus, and are complementary to the RNA transcribed from the sense strand. Common techniques including microarray approach and analysis of transcriptome databases are the major ways to globally identify cis-NATs in various eukaryotic organisms. Genome-wide in silico analysis has identified a large number of cis-NATs that may generate endogenous short interfering RNAs (nat-siRNAs), which participate in important biogenesis mechanisms for transcriptional and post-transcriptional regulation in rice. However, the transcriptomes are yet to be deeply sequenced to comprehensively investigate cis-NATs. Results: We applied high-throughput strand-specific complementary DNA sequencing technology (ssRNA-seq) to deeply sequence mRNA for assessing sense and antisense transcripts that were derived under salt, drought and cold stresses, and normal conditions, in the model plant rice (Oryza sativa). Combined with RAP-DB genome annotation (the Rice Annotation Project Database build-5 data set), 76,013 transcripts corresponding to 45,844 unique gene loci were assembled, in which 4873 gene loci were newly identified. Of 3819 putative rice cis-NATs, 2292 were detected as expressed and giving rise to small RNAs from their overlapping regions through integrated analysis of ssRNA-seq data and small RNA data. Among them, 503 cis-NATs seemed to be associated with specific conditions. The deep sequence data from isolated epidermal cells of rice seedlings further showed that 54.0% of cis-NATs were expressed simultaneously in a population of homogenous cells. Nearly 9.7% of rice transcripts were involved in one-to-one or many-to-many cis-NATs formation. Furthermore, only 17.4-34.7% of 223 many-to-many cis-NAT groups were all expressed and generated nat-siRNAs, indicating that only some cis-NAT groups may be involved in complex regulatory networks. Conclusions: Our study profiles an abundance of cis-NATs and nat-siRNAs in rice. These data are valuable for gaining insight into the complex function of the rice transcriptome.