Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein

Background: Though n-butanol has been proposed as a potential transportation biofuel, its toxicity oftencauses oxidative stress in the host microorganism and is considered one of the bottlenecks preventing itsefficient mass production.Results: To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengersfor reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT),mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed thegreatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, andnickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress.Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging butalso regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion proteincould contribute in an enhancement of the host microorganism’s growth rate.Conclusions: The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli wereexamined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein,OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These resultspresented indicate potential novel approaches for engineering stress tolerant microorganism strains

An Exploration On The Development Of The IT Management System In Taiwans Banking Industry: From The Marketing Perspectives

The focal point adopted in the present study is Customer Relationship Management (CRM) and its adoption in Taiwans banking industry. Since the current challenge banks are facing is in implementing and supporting new technological solutions that will enable them to be more responsive and flexible to their clients, a quantitative research methodology was employed in the present study in an attempt to answer the following research question: What are the critical factors that explain the degree of success in the deployment of CRM systems in Taiwans banking industry? First, based on the findings from the previous studies, an exploratory study consisting of focus-group interviews was conducted to uncover the nature of the problems confronting the banks in adopting CRM. Second, based on the findings from this preliminary investigation, a quantitative analysis using survey and statistical methods was conducted to identify possible answers to the research question. The research done with the present study has uncovered a number of factors which can be used to guide companies for a successful CRM deployment. These factors include primacy of customer service, customizing CRM functions/modules, discovering customers needs, maintaining employees moral, conducting a decision support system. If the major goal of implementing a CRM system is to improve the overall CRM deployment, the management in Taiwans banking industry should then emphasize three of two factors: primacy of customer service and customizing CRM functions/modules

A Bayesian measurement error model for two-channel cell-based RNAi data with replicates

RNA interference (RNAi) is an endogenous cellular process in which small double-stranded RNAs lead to the destruction of mRNAs with complementary nucleoside sequence. With the production of RNAi libraries, large-scale RNAi screening in human cells can be conducted to identify unknown genes involved in a biological pathway. One challenge researchers face is how to deal with the multiple testing issue and the related false positive rate (FDR) and false negative rate (FNR). This paper proposes a Bayesian hierarchical measurement error model for the analysis of data from a two-channel RNAi high-throughput experiment with replicates, in which both the activity of a particular biological pathway and cell viability are monitored and the goal is to identify short hair-pin RNAs (shRNAs) that affect the pathway activity without affecting cell activity. Simulation studies demonstrate the flexibility and robustness of the Bayesian method and the benefits of having replicates in the experiment. This method is illustrated through analyzing the data from a RNAi high-throughput screening that searches for cellular factors affecting HCV replication without affecting cell viability; comparisons of the results from this HCV study and some of those reported in the literature are included.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS496 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

The Impact of Single Session Intermittent Theta-Burst Stimulation over the Dorsolateral Prefrontal Cortex and Posterior Superior Temporal Sulcus on Adults with Autism Spectrum Disorder

Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) to explore its impact in adults with autism spectrum disorder (ASD). Among 25 adults with ASD, 19 (mean age: 20.8 years) completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation) in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT) and the Wisconsin Card Sorting Test (WCST). Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Social Responsiveness Scale (SRS). In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71) while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations

Survivin counteracts the therapeutic effect of microtubule de-stabilizers by stabilizing tubulin polymers

<p>Abstract</p> <p>Background</p> <p>Survivin is a dual function protein. It inhibits the apoptosis of cells by inhibiting caspases, and also promotes cell growth by stabilizing microtubules during mitosis. Over-expression of survivin has been demonstrated to induce drug-resistance to various chemo-therapeutic agents such as cisplatin (DNA damaging agent) and paclitaxel (microtubule stabilizer) in cancers. However, survivin-induced resistance to microtubule de-stabilizers such as <it>Vinca </it>alkaloids and Combretastatin A-4 (CA-4)-related compounds were seldom demonstrated in the past. Furthermore, the question remains as to whether survivin plays a dominant role in processing cytokinesis or inhibiting caspases activity in cells treated with anti-mitotic compounds. The purpose of this study is to evaluate the effect of survivin on the resistance and susceptibility of human cancer cells to microtubule de-stabilizer-induced cell death.</p> <p>Results</p> <p>BPR0L075 is a CA-4 analog that induces microtubule de-polymerization and subsequent caspase-dependent apoptosis. To study the relationship between the expression of survivin and the resistance to microtubule de-stabilizers, a KB-derived BPR0L075-resistant cancer cell line, KB-<it>L30</it>, was generated for this study. Here, we found that survivin was over-expressed in the KB-<it>L30 </it>cells. Down-regulation of survivin by siRNA induced hyper-sensitivity to BPR0L075 in KB cells and partially re-stored sensitivity to BPR0L075 in KB-<it>L30 </it>cells. Western blot analysis revealed that down-regulation of survivin induced microtubule de-stabilization in both KB and KB-<it>L30 </it>cells. However, the same treatment did not enhance the down-stream caspase-3/-7 activities in BPR0L075-treated KB cells. Translocation of a caspase-independent apoptosis-related molecule, apoptosis-inducing factor (AIF), from cytoplasm to the nucleus was observed in survivin-targeted KB cells under BPR0L075 treatment.</p> <p>Conclusion</p> <p>In this study, survivin plays an important role in the stability of microtubules, but not with caspases inhibition. Over-expression of survivin counteracts the therapeutic effect of microtubule de-stabilizer BPR0L075 probably by stabilizing tubulin polymers, instead of the inhibition of caspase activity in cancer cells. Besides microtubule-related caspase-dependent cell death, caspase-independent mitotic cell death could be initiated in survivin/BPR0L075 combination treatments. We suggest that combining microtubule de-stabilizers with a survivin inhibitor may attribute to a better clinical outcome than the use of anti-mitotic monotherapy in clinical situations.</p

Microstructure of non-polar GaN on LiGaO2 grown by plasma-assisted MBE

We have investigated the structure of non-polar GaN, both on the M - and A-plane, grown on LiGaO2 by plasma-assisted molecular beam epitaxy. The epitaxial relationship and the microstructure of the GaN films are investigated by transmission electron microscopy (TEM). The already reported epi-taxial relationship and for M -plane GaN is confirmed. The main defects are threading dislocations and stacking faults in both samples. For the M -plane sample, the density of threading dislocations is around 1 × 1011 cm-2 and the stacking fault density amounts to approximately 2 × 105 cm-1. In the A-plane sample, a threading dislocation density in the same order was found, while the stacking fault density is much lower than in the M -plane sample

Risk factors and 180-day mortality of acute kidney disease in critically ill patients: A multi-institutional study

BackgroundCritically ill patients with acute kidney injury (AKI) have a poor prognosis. Recently, the Acute Disease Quality Initiative (ADQI) proposed to define acute kidney disease (AKD) as acute or subacute damage and/or loss of kidney function post AKI. We aimed to identify the risk factors for the occurrence of AKD and to determine the predictive value of AKD for 180-day mortality in critically ill patients.MethodsWe evaluated 11,045 AKI survivors and 5,178 AKD patients without AKI, who were admitted to the intensive care unit between 1 January 2001 and 31 May 2018, from the Chang Gung Research Database in Taiwan. The primary and secondary outcomes were the occurrence of AKD and 180-day mortality.ResultsThe incidence rate of AKD among AKI patients who did not receive dialysis or died within 90 days was 34.4% (3,797 of 11,045 patients). Multivariable logistic regression analysis indicated that AKI severity, underlying early CKD, chronic liver disease, malignancy, and use of emergency hemodialysis were independent risk factors of AKD, while male gender, higher lactate levels, use of ECMO, and admission to surgical ICU were negatively correlated with AKD. 180-day mortality was highest among AKD patients without AKI during hospitalization (4.4%, 227 of 5,178 patients), followed by AKI with AKD (2.3%, 88 of 3,797 patients) and AKI without AKD (1.6%, 115 of 7,133 patients). AKI with AKD had a borderline significantly increased risk of 180-day mortality (aOR 1.34, 95% CI 1.00–1.78; p = 0.047), while patients with AKD but no preceding AKI episodes had the highest risk (aOR 2.25, 95% CI 1.71–2.97; p &lt; 0.001).ConclusionThe occurrence of AKD adds limited additional prognostic information for risk stratification of survivors among critically ill patients with AKI but could predict prognosis in survivors without prior AKI

Transmission of acute infectious illness among cases of Kawasaki disease and their household members

Background/purposeKawasaki disease (KD) is a disease of unknown cause and the causative agent is most likely to be infectious in nature. To investigate the household transmission pattern of infectious illness and etiology, we thus initiated a prospective case and household study.MethodsWe enrolled KD cases and their household members from February 2004 to September 2008. The KD cases and their household members accepted questionnaire-based interviews of the contact history, signs of infection, and symptoms to check whether clusters of infectious illness occurred.ResultsA total of 142 KD cases and 561 household members were enrolled. Among the 142 KD cases, 136 cases (96%) were typical KD, and six (4%) were atypical KD. Of the 561 household members, 17% were siblings, 46% were parents, 18% were grandparents, and the others were cousins or babysitters. Prior to the onset of their KD illness, 66% (94/142) KD cases had contact with ill household members. On the same day of the onset of KD cases' illness, 4% (6/142) KD cases had household members with illness. After KD cases' disease onset, 70% (100/142) KD cases had at least one other family member with illness. Overall, 61% (343/561) of all the household members had acute infectious illness during KD cases' acute stage, and 92% (130/142) of the families had clusters of infectious illness.ConclusionA total of 66% KD cases had positive contact with ill household members prior to their disease onset and 92% of families had clusters of infectious illness, so KD is strongly associated with infections