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This research sought to explore how teaching utilizing a marine science-related board game affected students' motivation, interest, and achievement in marine science learning at the high school level. The research utilized an experimental design with pre-test and post-test measurements and a classroom setting, and included an experimental group containing 25 students and a control group containing 26 students. The experiment was carried out over the course of 12 lessons, with various questionnaires, including a marine science learning motivation (MSLM) inventory, a marine science learning interest (MSLI) inventory, and a marine science learning achievement (MSLA) inventory, being used as the measurement instruments. The research analysed the students' scores on these inventories using one-way analysis of ANCOVA. The main results of this research were as follows: 1) with regard to the MSLM inventory, the 'relevance', 'confidence', and 'total score' were significantly different between the two groups; 2) with regard to the MSLI inventory, the 'cognitions regarding marine science' were significantly different between the two groups; and 3) with regard to the MSLA, all of the dimensions including 'memory', 'understanding', 'high-level thinking', and 'total score' were significantly different between the two groups.

Glutathione redox cycling is important for cell cycle regulation, but its mechanisms are not well understood. We previously identified a small‐sized mutant, suppressor of mat3 15‐1 (smt15‐1) that has elevated cellular glutathione. Here, we demonstrated that SMT15 is a chloroplast sulphate transporter. Reducing expression of γ‐GLUTAMYLCYSTEINE SYNTHETASE, encoding the rate‐limiting enzyme required for glutathione biosynthesis, corrected the size defect of smt15‐1 cells. Overexpressing GLUTATHIONE SYNTHETASE (GSH2) recapitulated the small‐size phenotype of smt15‐1 mutant, confirming the role of glutathione in cell division. Hence, SMT15 may regulate chloroplast sulphate concentration to modulate cellular glutathione levels. In wild‐type cells, glutathione and/or thiol‐containing molecules (GSH/thiol) accumulated in the cytosol at the G1 phase and decreased as cells entered the S/M phase. While the cytosolic GSH/thiol levels in the small‐sized mutants, smt15‐1 and GSH2 overexpressors, mirrored those of wild‐type cells (accumulating during G1 and declining at early S/M phase), GSH/thiol was specifically accumulated in the basal bodies at early S/M phase in the small‐sized mutants. Therefore, we propose that GSH/thiol‐mediated redox signalling in the basal bodies may regulate mitotic division number in Chlamydomonas reinhardtii. Our findings suggest a new mechanism by which glutathione regulates the multiple fission cell cycle in C. reinhardtii. Summary Statement: The cell cycle is associated with periodic oscillation of the cellular redox environment. Our investigation of subcellular glutathione and thiol‐containing molecules in Chlamydomonas reinhardtii has provided new insights into their role in regulating the cell cycle. [ABSTRACT FROM AUTHOR]

Social class stagnation is a current topic of concern. The stagnation of generational mobility could result in society losing its ability to enhance individuals’ social status. This study explored higher education expansion as a possible cause of class stagnation by adopting the Human Development Index as a comprehensive indicator of individual social status, and determined dynamic mobility by observing the case of Taiwan, where higher education was expanded in 1994. Pseudo-panel data were obtained from the Family Income and Expenditure Survey. Our results indicate that rapid higher education expansion has a negative impact on social mobility for the generation who enters the labor market after the expansion starting point.

The development of standards, or indicators, for global/international education has lagged behind that of the national curriculum. To address this, we developed a set of core concepts and competence indicators of global/international education for Taiwan's "Grade 1-9 Curriculum Guidelines" and revised these through three rounds of Delphi surveys. The final version is composed of five core concepts, three dimensions, and 60 competence indicators across seven learning areas accessed through four learning stages. To explore the extent to which the national curriculum overlaps with global/international education, we conducted content analysis to examine the global/international components of the guidelines. This revealed that 10.70% of the competence indicators in the guidelines were related to global core concepts. Numerous indicators were related to multiculture, whereas only a few were related to human rights and social justice. The comparison of the indicators for learning areas showed that integrative activities indicators were the most closely related to global education, whereas social studies indicators were related to all global core concepts. The mathematics indicators were unintegrated with global core concepts, with most of the learning areas emphasizing only one or two such concepts.

The issue of how youth are motivated to prepare for their careers has been longstanding, yet studies in this area remain limited. This study examines the effect of labor market risk, such as wages and unemployment, on the career preparedness of young people, taking the example of Taiwan. Multi-year cross-sectional data from a manpower utilization survey and higher education survey were used, and logit models, including the multilevel-multinomial logit model and ordered models, were employed to analyze the empirical data. The findings suggest that youth career preparation is positively affected by market risk variables. Additionally, school participation and parental employment status appear to play important roles in determining the career preparedness of young people. It is essential that sustainable development is enabled so that today's youth can develop the skills and capabilities necessary for a prosperous future. [ABSTRACT FROM AUTHOR]

This paper investigates the effects of employment protection legislation on the rates of hiring, separation, worker flows, job reallocation, and churning flows for the case of Taiwan. Our empirical identification takes advantage of a reform created by Taiwan's enactment of Labor Standards Law, which has substantially increased the costs of firing, and the implementation of the law's enforcement measures. Moreover, our identification also exploits the fact that the stringency of the law's provisions and the intensity of the law's enforcement vary with establishment size. On the basis of the monthly data at the establishment level for the period 1983-1995, we find that Taiwan's Labor Standards Law and its enforcement measures have dampened labor turnover for medium-sized and large establishments, while that of small establishments was not affected. (JEL J65, J63, J88), I. INTRODUCTION This paper studies the effects of employment protection legislation (EPL) on the rates of hiring, separation, worker flows, job reallocation, and churning flows. EPL refers to restrictions on [...]

Background: Medical versus surgical management of pediatric periorbital infection secondary to acute bacterial rhinosinusitis (ABRS) can be a dilemma for clinicians. This study aimed to evaluate the prognostic factors related to the need for surgical drainage and to help direct management decisions. Methods: Children admitted for periorbital infection secondary to ABRS between 2001 and 2019 were retrospectively reviewed. Demographics, clinical presentations, laboratory data, comorbidities, and computed tomography results were collected from medical records. Results: A total of 141 pediatric patients were enrolled. Forty-two patients (29.8%) required surgical intervention. Multivariate logistic regression analysis identified that delayed initiation of intravenous antibiotics from the onset of periorbital swelling (odds ratio [OR] = 1.94; p < 0.001) and proptosis at initial presentation (OR = 6.63; p = 0.008) were significantly associated with the need for surgical intervention. A C-reactive protein value of > 55.73 mg/L and initiation of intravenous antibiotic treatment > 2 days from the onset of periorbital swelling showed the best predictive power for surgery. Conclusions: Pediatric patients with delayed initiation of intravenous antibiotic treatment and initial presentation of proptosis had worse outcomes and required surgical intervention. [ABSTRACT FROM AUTHOR]

Small ubiquitin‐like modifier (SUMO) conjugation, or SUMOylation, is a reversible post‐translational modification that is important for regulation of many cellular processes including cell division cycle in the eukaryotic kingdom. However, only a portion of the components of the Chlamydomonas SUMOylation system are known and their functions and regulation investigated. The present studies are aimed at extending discovery and characterization of new components and improving the annotation and nomenclature of all known proteins and genes involved in the system. Even though only one copy of the heterodimerized SUMO‐activating enzyme, SAE1 and SAE2, was identified, the number of SUMO‐conjugating enzymes (SCEs) and SUMO proteases/isopeptidase was expanded in Chlamydomonas. Using the reconstituted SUMOylation system, we showed that SCE1, SCE2, and SCE3 have SUMO‐conjugating activity. In addition to SUMOylation, components required for other post‐translational modifications such as NEDDylation, URMylation, and UFMylation, were confirmed to be present in Chlamydomonas. Our data also showed that besides isopeptidase activity, the SUMO protease domain of SUPPRESSOR OF MAT3 7/SENTRIN‐SPECIFIC PROTEASE 1 (SMT7/SENP1) has endopeptidase activity that is capable of processing SUMO precursors. Moreover, the key cell cycle regulators of Chlamydomonas E2F1, DP1, CDKG1, CYCD2, and CYCD3 were SUMOylated in vitro, suggesting SUMOylation may be part of regulatory pathway modulating cell cycle regulators. [ABSTRACT FROM AUTHOR]

Proliferating cells actively coordinate growth and cell division to ensure cell-size homeostasis; however, the underlying mechanism through which size is controlled is poorly understood. Defect in a SUMO protease protein, suppressor of mat3 7 (SMT7), has been shown to reduce cell division number and increase cell size of the small-size mutant mating type locus 3-4 (mat3-4), which contains a defective retinoblastoma tumor suppressor-related protein of Chlamydomonas (Chlamydomonas reinhardtii). Here we describe development of an in vitro SUMOylation system using Chlamydomonas components and use it to provide evidence that SMT7 is a bona fide SUMO protease. We further demonstrate that the SUMO protease activity is required for supernumerous mitotic divisions of the mat3-4 cells. In addition, we identified RIBOSOMAL PROTEIN L30 (RPL30) as a prime SMT7 target and demonstrated that its SUMOylation is an important modulator of cell division in mat3-4 cells. Loss of SMT7 caused elevated SUMOylated RPL30 levels. Importantly, overexpression of the translational fusion version of RPL30-SUMO4, which mimics elevation of the SUMOylated RPL30 protein in mat3-4 , caused a decrease in mitotic division and recapitulated the size-increasing phenotype of the smt7-1 mat3-4 cells. In summary, our study reveals a novel mechanism through which a SUMO protease regulates cell division in the mat3-4 mutant of Chlamydomonas and provides yet another important example of the role that protein SUMOylation can play in regulating key cellular processes, including cell division. [ABSTRACT FROM AUTHOR]

Highlights • Magnetic nanoparticles as contrast agent for dynamic susceptibility contrast MRI. • Perfusion MRI parameters can reflect properties of magnetic nanoparticles. • Size of magnetic nanoparticles is the dominate factor to affect perfusion parameters. • PEGylation may affect perfusion parameters for small-sized particles. • Magnetic nanoparticles are feasible for renal perfusion evaluation. Abstract Magnetic nanoparticles (MNPs) can be used as magnetic resonance imaging (MRI) contrast agent with dynamic susceptibility contrast (DSC) MRI, which is an important in vivo method to assess organ perfusion with multiple clinical applications. Since variations in particle size and PEGylation of MNPs may potentially influence particle-tissue interactions in the microcirculation, we evaluate their effects on rat kidneys with DSC MRI. Anesthetized Sprague Dawley rats were cannulated for intravenous injection of dextran-coated MNPs (50 nm and 250 nm; 5 mg/kg) with or without PEGylation during acquirement of DSC MRI images. The results demonstrate that both particle size and PEGylation may alter perfusion parameters. Relative mean transit time (rMTT) of 50 nm particles is 1.8 fold of that of 250 nm particles with or without PEGylation. In MNPs of 50 nm, PEGylation is associated with 38% and 25% shorter time-to-peak (TTP) and time from onset to 50% drop from peak (T50), respectively; however, PEGylation exerts no effect on these parameters of 250 nm particles. Nevertheless, particle size or PEGylation exert no influence on the prediction of relative blood flow or relative blood volume of the kidney. In conclusion, DSC MRI is a feasible method to evaluate renal perfusion and properties of MNPs in circulation. [ABSTRACT FROM AUTHOR]

We report the preparation of protofibrils from oligomeric Aβ40 aggregates, which have been incubated under spatially constrained conditions. The molecular structure of the resultant protofibrils is highly homogeneous, suggesting that the phenomenon of structural polymorphism commonly observed in Aβ40 fibrils may be largely due to multiple nucleation events. [ABSTRACT FROM AUTHOR]

In recent years, service industries in many countries have grown rapidly and now play an important role in national employment and GDP; moreover, as living standards have risen, intangible service qualities have become increasingly important. Thus, as one of the closest commercial links to consumers, department stores should strive to enhance the quality of their services to attract and retain customers and to maintain their competitiveness. In this study, the Retail Service Quality Scale was adopted and the Kano and Refined Kano models were applied to extract service-quality factors; then, the importance-satisfaction (I-S) model was used to clarify the service-quality factors to be improved before employing the theory of inventive problem-solving method to measure innovation. Finally, the service-quality and quality factors falling in the I-S model's excellent area were imported into quality function deployment using the voice of the customer process to establish a department-store house of quality for innovative service. Based on its empirical results, this study proposes a general framework for innovative service-quality for department stores to use in formulating service innovation strategies. The findings and developed framework will improve the performance of department stores by enhancing the quality of service. [ABSTRACT FROM AUTHOR]

The report describes the synthesis of degradable, pH-sensitive, membrane-destabilizing, star-shaped polymers where copolymers of hydrophobic hexyl methacrylate (HMA) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomers are grafted from the secondary face of a beta-cyclodextrin (β-CD) core via acid-labile hydrazone linkages using atom transfer radical polymerization. The effect of the graft's molecular weight, HMA/DMAEMA molar ratio, and the fraction of DMAEMA converted to cationic N,N,N-trimethylaminoethyl methacrylate (TMAEMA) monomers on polymer's transfection capacity is systematically investigated. Results show that all star-shaped polymers condense anti-GAPDH silencing RNA (siRNA) into nanosized particles at +/- ratio ≤ 4:1. Star polymers with shorter (25kDa) P(HMA- co-DMAEMA- co-TMAEMA) grafts are more efficient and less cytotoxic than carriers with longer (40kDa) grafts. The results show that increasing the ratio of hydrophobic HMA monomers in graft's composition higher than 50 mole% dramatically reduces polymer's aqueous solubility and abolishes their transfection capacity. Further, retention of DMAEMA monomers in graft's composition provide a buffering capacity that enhanced the endosomal escape and transfection capacity of the polymers. These systematic studies show that β-CD-P(HMA- co-DMAEMA- co-TMAEMA)4.8 polymer with a 25 kDa average graft's molecular weight and a 50/25/25 ratio of HMA/DMAEMA/TMAEMA monomers is the most efficient carrier in delivering the siRNA cargo into the cytoplasm of epithelial cancer cells. [ABSTRACT FROM AUTHOR]

This study investigates the effects of employment protection on wages. The implementation of employment protection legislation increases employers' firing costs and reduces labor turnover, and, therefore, results in lower wages. Our empirical results show that the implementation of Taiwan's leads to a reduction in wages, the effects of which varies with the stringency of the law's enforcement. In addition, employment protection can lead to a decrease in wage dispersion, implying the worsening of job matches. [ABSTRACT FROM AUTHOR]

Cationic polymers such as poly(amidoamine), PAMAM, dendrimers have been used to electrostatically complex siRNA molecules forming dendriplexes for enhancing the cytoplasmic delivery of the encapsulated cargo. However, excess PAMAM dendrimers is typically used to protect the loaded siRNA against enzymatic attack, which results in systemic toxicity that hinders the in vivo use of these particles. In this paper, we evaluate the ability of G4 (flexible) and G5 (rigid) dendrimers to complex model siRNA molecules at low +/− ratio of 2/1 upon incubation for 20 minutes and 24 hours. We examine the ability of the formed G4 and G5 dendriplexes to shield the loaded siRNA molecules and protect them from degradation by RNase V1 enzymes using atomic force microscopy (AFM). Results show that G4 and G5 dendrimers form similar hexagonal complexes upon incubation with siRNA molecules for 20 minutes with average full width of 43±19.3 nm and 62±8.3 at half the maximum height, respectively. AFM images show that these G4 and G5 dendriplexes were attacked by RNase V1 enzyme leading to degradation of the exposed RNA molecules that increased with the increase in incubation time. In comparison, incubating G4 and G5 dendrimers with siRNA for 24 hours led to the formation of large particles with average full width of 263±60 nm and 48.3±2.5 nm at half the maximum height, respectively. Both G4 and G5 dendriplexes had a dense central core that proved to shield the loaded RNA molecules from enzymatic attack for up to 60 minutes. These results show the feasibility of formulating G4 and G5 dendriplexes at a low N/P (+/−) ratio that can resist degradation by RNase enzymes, which reduces the risk of inducing non-specific toxicity when used in vivo. [ABSTRACT FROM AUTHOR]

Chinese is one of the most important global languages, but at some universities of science and technology, Chinese-language learning is unfortunately not valued by students. According to the results of the Program for International Student Assessment (PISA), organized by the United Nations every three years, although Taiwanese students' performance in reading improved from 2015 to 2018, many problems remain in the teaching field that lead to a lack of student interest in Chinese-language learning. We attempted to use flipped teaching to intervene in the Chinese-language curriculum at the university of science and technology at which we teach. This methodological process and procedure was used to plan teaching materials, and 36 weeks of teaching with a Chinese-language curriculum were offered to freshman students in one academic year. We then evaluated teaching effectiveness through the pre- and post-tests of students' language proficiency, obtained feedback from students through school-wide teaching evaluation questions, reviewed the teaching effectiveness of the Chinese-language curriculum for the academic year, and achieved significant improvements in students' reading skills with regard to language learning. [ABSTRACT FROM AUTHOR]

Ocean sustainability and resource use are emphasized globally. The primary goal of ocean preservation is to enhance citizens' ocean literacy. In this study, cluster sampling was conducted on students from seven public middle schools in Taiwan to investigate their use of ocean literacy concept words, propositional sentences, and knowledge sources. Qualitative analysis, descriptive statistics, and one-way analysis of variance were conducted on 496 valid questionnaires. The middle school students exhibited an accuracy rate of 63% for ocean literacy sentence-making, which indicated a basic level of performance. The students commonly used terms such as "ocean," "Atlantic Ocean," and "tsunami." Students had common misconceptions when using the terms "sea level rising," "Kuroshio current," and "tsunami." In addition, students who were female, in a higher grade, and who attended a coastal school had higher ocean literacy scores. The students' primary sources of ocean literacy knowledge were museums and television. Through an analysis students' use of ocean concept words and misconceptions, the aim of this study was to enhance the implementation efficiency of marine education to cultivate students' ocean literacy. [ABSTRACT FROM AUTHOR]

Background: Magnesium alloy implants have lower stress load and can be absorbed gradually, but their degradation rates are too fast generally. A magnesium alloy contained 5% Zn and 0.5% Zr (ZK50) which have lower degradation rate are designed to be applied to cannulated bone screw.Methods: An oxidation heat treatment of 380 °C for 2 h proceeds to modify the ZK50 Mg alloy (ZK50-H). The microstructure observation, degradation tests and Biocompatibility analysis are proceeded between ZK50 and ZK50-H. Finally, a mini-pig implantation test is proceeded to provide a reference of implant application for future pre-clinical evaluation.Results: The heat treatment can improve the mechanical properties. A passive ceramic layer formed after simulated body fluid (SBF) solution immersion can restrict the degradation effectively. The cytotoxicity test shows the initial biosafety of ZK50 Mg alloy. A mini-pig implantation test of bone screw has proceeded to confirm the advanced biocompatibility. The ZK50-H screws can maintain enough support at least 8 weeks which the fracture of bone can get curing. The excellent osteoinduction of ZK50-H has a positive effect to growth of new bones and help the mini-pig regain heal faster in 12 weeks.Conclusion: This study shows ZK50-H Mg alloy screw is a feasible degradation implant and can be carried out the next-step clinical experiments. [ABSTRACT FROM AUTHOR]

An abstract of the article "Effect of functional foot orthotics on golf swing stability and accuracy of shots" by Chun-Ju Chang, Sai-Wei Yang, Ching-Wei Chang, Yen-Ling Lin, Fan-Chih Kuo, Che-Chang Lin, and Keh-Tao Liu is presented.

Sunitinib, a multitargeted receptor Y kinase inhibitor (TKI) used for the treatment of renal cell carcinoma and gastrointestinal stromal tumor (GIST), is notorious for cutaneous adverse effects, such as hand-foot skin reaction (HFSR). To explore the underlying mechanism of HFSR, we enrolled 53 sunitinib-treated GIST patients, including 23 HFSR cases, and 30 tolerant controls. Among the 29 biomarkers examined, soluble FasL (sFasL) showed significant increase in the plasma, blister fluids, and skin lesions of HFSR patients. The plasma levels of sFasL were significantly correlated with those of sunitinib in HFSR patients. In addition to FasL, augmented expression of Fas and active caspase 3 was also detected in the epidermis of HFSR patients. The increased FasL caused keratinocyte death, as the use of anti-FasL antibody specifically blocked cell apoptosis. Oral administration of sunitinib to mice increased skin susceptibility to mechanical injuries in a dose/time-dependent manner. The administration of sunitinib (40 mg kg−1 per day) for 4 weeks to mice caused the maximally affected skin area with an erosion-to-ulceration response to tape-stripping. The skin biopsies of mice administered sunitinib exhibited increased expression of Fas and FasL in the apoptotic keratinocytes in the epidermis. Our data revealed that Fas/FasL interaction mediates keratinocyte death in sunitinib-induced HFSR. [ABSTRACT FROM AUTHOR]

Iron is an essential micronutrient for various bacterial cellular processes. Fur is a global transcriptional regulator participating in iron homeostasis. Stenotrophomonas maltophilia is a ubiquitous environmental bacterium that has emerged as an opportunistic pathogen. To elucidate the novel regulatory mechanism behind iron homeostasis in S. maltophilia, wild-type KJ and KJΔFur, a fur mutant, were subjected to transcriptome assay. A five-gene cluster, sbiBA-sbiTRS , was significantly upregulated in KJΔFur. SbiAB is an ATP type efflux pump, SbiT is an inner membrane protein, and SbiSR is a two-component regulatory system (TCS). The sbiTRS operon organization was verified by reverse transcription-PCR (RT-PCR). Localization prediction and bacterial two-hybrid studies revealed that SbiT resided in the inner membrane and had an intramembrane interaction with SbiS. In iron-replete conditions, SbiT interacted with SbiS and maintained SbiSR TCS in a resting state. In response to iron depletion stress, SbiT no longer interacted with SbiS, leading to SbiSR TCS activation. The iron source utilization assay demonstrated the contribution of SbiSR TCS to stenobactin-mediated ferric iron utilization but notto the utilization of hemin and ferric citrate. Furthermore, SmeDEF and SbiAB pumps, known stenobactin secretion outlets, were members of the SbiSR regulon. Collectively, in an iron-depleted condition, SbiSR activation is regulated by Fur at the transcriptional level and by SbiT at the posttranslational level. Activated SbiSR contributes to stenobactin-mediated ferric iron utilization by upregulating the smeDEF and sbiAB operons. SbiSR is the first TCS found to be involved in iron homeostasis in S. maltophilia. IMPORTANCE Therapeutic options for Stenotrophomonas maltophilia infections are limited because S. maltophilia is intrinsically resistant to several antibiotics. Iron is an essential element for viability, but iron overload is a lethal threat to bacteria. Therefore, disruption of iron homeostasis can be an alternative strategy to cope with S. maltophilia infection. The intricate regulatory networks involved in iron hemostasis have been reported in various pathogens; however, little is known about S. maltophilia. Herein, a novel sbiTRS operon, a member of Fur regulon, was characterized. SbiT, an inner membrane protein, negatively modulated the SbiSR two-component regulatory system by intramembrane protein-protein interaction with SbiS. In response to iron-depleted stress, SbiSR was activated via the regulation of Fur and SbiT. Activated SbiSR upregulated smeDEF and sbiAB , which contributed to stenobactin-mediated ferric iron utilization. A novel fur-sbiT-sbiSR-smeDEF/sbiAB regulatory circuit in S. maltophilia was revealed.

Objectives: Weight gain and metabolic disturbances such as dyslipidemia, are frequent side effects of second-generation antipsychotics, including olanzapine. This study examined the metabolic effects of chronic olanzapine exposure. In addition, we investigated the hepatic fatty acid effects of olanzapine in female C57BL/6J mice fed a normal diet., Materials and Methods: Female C57BL/6J mice orally received olanzapine or normal saline for 7 weeks. The effects of long-term olanzapine exposure on body weight changes, food efficiency, blood glucose, triglyceride (TG), insulin, and leptin levels were observed. Hepatic TG and abdominal fat mass were investigated, and fat cell morphology was analyzed through histopathological methods. The levels of protein markers of fatty acid regulation in the liver, namely fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), were measured., Results: Olanzapine treatment increased the food intake of the mice as well as their body weight. Biochemical analyses showed that olanzapine increased blood TG, insulin, leptin, and hepatic TG. The olanzapine group exhibited increased abdominal fat mass and fat cell enlargement in abdominal fat tissue. Western blotting of the mouse liver revealed significantly higher (1.6-fold) levels of SCD-1 in the olanzapine group relative to the control group; by contrast, FAS levels in the two groups did not differ significantly., Conclusion: Enhanced lipogenesis triggered by increased hepatic SCD-1 activity might be a probable peripheral mechanism of olanzapine-induced dyslipidemia. Some adverse metabolic effects of olanzapine may be related to the disturbance of lipid homeostasis in the liver.

Short interfering RNA (siRNA) targeted against anti-apoptotic Bcl-2 protein proved to knockdown its expression and trigger cancer cell death. We used degradable, pH-sensitive, comb-like [P(EAA-co-BMA)-b-PNASI-g-P(HMA-co-TMAEMA)] polymer to condense anti-Bcl-2 siRNA into "smart" particles, which proved to shuttle their cargo past the endosomal membrane and into the cytoplasm of HeLa and UM-SCC-17B cancer cells. HeLa and UM-SCC-17B cancer cells were treated with anti-Bcl-2 particles followed by quantifying Bcl-2 mRNA and protein levels using qRT-PCR and western blotting, respectively. "Smart" anti-Bcl-2 particles selectively suppress Bcl-2 mRNA and protein levels in HeLa cells by 50%-60% and 79%-81%, respectively. Similarly, "smart" anti-Bcl-2 particles inhibited Bcl-2 mRNA levels by 30%, 40%, and 20% upon incubation with UM-SCC-17B cancer cells for 48, 72, and 96 h, respectively. Bcl-2 protein expression in UM-SCC-17B cancer cells was inhibited by 30% after treatment for 72 h. Results show that pH-sensitive comb-like polymer complex anti-Bcl-2 siRNA forming "smart" nanoparticles that deliver their cargo into the cytoplasm of HeLa and UM-SCC-17B cancer cells causing Bcl-2 knockdown at the mRNA and protein levels.

B-cell lymphoma 2 (Bcl-2) is an antiapoptotic protein that is overexpressed in head and neck squamous cell carcinomas, which has been implicated in development of radio- and chemoresistance. Small molecule inhibitors such as AT-101 (a BH3-mimetic drug) have been developed to inhibit the antiapoptotic activity of Bcl-2 proteins, which proved effective in restoring radio- and chemo-sensitivity in head and neck cancer cells. However, high doses of AT-101 are associated with gastrointestinal, hepatic, and fertility side effects, which prompted the search for other Bcl-2 inhibitors. Short interfering RNA (siRNA) proved to inhibit antiapoptotic Bcl-2 protein expression and trigger cancer cell death. However, transforming siRNA molecules into a viable therapy remains a challenge due to the lack of efficient and biocompatible carriers. We report the development of degradable star-shaped polymers that proved to condense anti-Bcl-2 siRNA into "smart" pH-sensitive and membrane-destabilizing particles that shuttle their cargo past the endosomal membrane and into the cytoplasm of head and neck cancer cells. Results show that "smart" anti-Bcl-2 particles reduced the mRNA and protein levels of antiapoptotic Bcl-2 protein in UM-SCC-17B cancer cells by 50-60% and 65-75%, respectively. Results also show that combining "smart" anti-Bcl-2 particles with the IC25 of AT-101 (inhibitory concentration responsible for killing 25% of the cells) synergistically inhibits cancer cell proliferation and increases cell apoptosis, which reduce the survival of UM-SCC-17B cancer cells compared to treatment with AT-101 alone. Results indicate the therapeutic benefit of combining siRNA-mediated knockdown of antiapoptotic Bcl-2 protein expression with low doses of AT-101 for inhibiting the growth of head and neck cancer cells.

Gram-positive bacteria of the genus Streptomyces possess linear chromosomes and linear plasmids capped by terminal proteins covalently bound to the 5' ends of the DNA. The linearity of Streptomyces chromosomes raises the question of how they are transferred during conjugation, particularly when the mobilizing plasmids are also linear. The classical rolling circle replication model for transfer of circular plasmids and chromosomes from an internal origin cannot be applied to this situation. Instead it has been proposed that linear Streptomyces plasmids mobilize themselves and the linear chromosomes from their telomeres using terminal-protein-primed DNA synthesis. In support of this 'end first' model, we found that artificially circularized Streptomyces chromosomes could not be mobilized by linear plasmids (SLP2 and SCP1), while linear chromosomes could. In comparison, a circular plasmid (pIJ303) could mobilize both circular and linear chromosomes at the same efficiencies. Interestingly, artificially circularized SLP2 exhibited partial self-transfer capability, indicating that, being a composite replicon, it may have acquired the additional internal origin of transfer from an ancestral circular plasmid during evolution.

Recombinant thermostable direct hemolysin from Grimontia hollisae (Gh-rTDH) exhibits paradoxical Arrhenius effect, where the hemolytic activity is inactivated by heating at 60 °C but is reactivated by additional heating above 80 °C. This study investigated individual or collective mutational effect of Tyr53, Thr59, and Ser63 positions of Gh-rTDH on hemolytic activity, Arrhenius effect, and biophysical properties. In contrast to the Gh-rTDH wild-type (Gh-rTDH(WT)) protein, a 2-fold decrease of hemolytic activity and alteration of Arrhenius effect could be detected from the Gh-rTDH(Y53H/T59I) and Gh-rTDH(T59I/S63T) double-mutants and the Gh-rTDH(Y53H/T59I/S63T) triple-mutant. Differential scanning calorimetry results showed that the Arrhenius effect-loss and -retaining mutants consistently exhibited higher and lower endothermic transition temperatures, respectively, than that of the Gh-rTDH(WT). Circular dichroism measurements of Gh-rTDH(WT) and Gh-rTDH(mut) showed a conspicuous change from a β-sheet to α-helix structure around the endothermic transition temperature. Consistent with the observation is the conformational change of the proteins from native globular form into fibrillar form, as determined by Congo red experiments and transmission electron microscopy.

Poly(amidoamine) (PAMAM) dendrimers are a family of water-soluble polymers with a characteristic tree-like branching architecture and a large number of surface groups, which have been used to immobilize a variety of therapeutic molecules for targeted drug delivery. Earlier studies showed that small cationic PAMAM-NH2 and selected anionic PAMAM-COOH dendrimers permeate across in vitro models of the small intestinal epithelium by paracellular and transcellular transport mechanisms. The focus of this research is to mathematically calculate the effect of cationic, anionic, and neutral PAMAM dendrimers on the porosity of epithelial tight junctions as a function of dendrimers concentration, incubation time, generation number, and charge density. Results show that the increase in the concentration, incubation time and generation number of cationic G0-G2 PAMAM-NH2 and anionic G2.5 and G3.5 PAMAM-COOH dendrimers caused a corresponding increase in the porosity of Caco-2 cell monolayers. Neutral G2-G4 PAMAM-OH dendrimers had no effect on the porosity of intestinal cells. These results provide quantitative evidence that the observed increase in permeability of PAMAM dendrimers across Caco-2 cell monolayers is due to their effect on the organization of the tight junctions and the associated increase in membrane porosity. Furthermore, these results emphasize the potential of cationic PAMAM-NH2 and anionic PAMAM-COOH dendrimers to function as carriers for controlled oral drug delivery.