LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding

The four members of the LRRTM family (LRRTM1-4) are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG) granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.Peer reviewe

Characterization of E. coli E38???s Persistence to Bacterial Predation

Department of Biological SciencesThe threat of multidrug-resistant bacteria is a major problem the world is facing currently. As many of the antibiotics available continue to fail at combating the ???superbugs???, the necessity of finding new methods or ways to combat them becomes a priority. As an alternative or supplement to chemical antibiotics, predatory bacteria, such as Bdellovibrio bacteriovorus, are thought to be promising candidates since they can prey on a wide range of the other gram-negative bacteria, including more than 100 human pathogens and antibiotic-resistant strains. However, some recent researchers have found that some bacterial strains appear to be resistant to predation by B. bacteriovorus, with no knowledge on the how or why. One such strain is the pathogen Escherichia coli E38. We found out that E. coli E38 appeared to be resistant to predation by cell viability test, however with cell viability assay and confocal microscopy, we also found that there was some level of predation occurred. This result is similar to that of antibiotic persisters in that the sub-population remains viable even in the presence of B. bacteriovorus. Bacteria persisters is a sub-population of bacteria that can survive from antibiotics without a genetic basis of resistance but due to metabolic/phenotypic variations within the entire population. These survivors are clinically important since they are relevant to chronic infection and relapse. Through further studies, we found that E. coli MG1655 antibiotic persisters (AP), which were induced by pre-treatment with antibiotics, were resistant to predation by B. bacteriovorus. Conversely, the sub-population of prey which survived predation, i.e., predation persisters (PP), were more resistant to antibiotics. Moreover, a starved population of E. coli E38 showed similar survival when exposed to antibiotics to predation persister while those of E. coli MG1655 did not. This demonstrates that the persistence tendency of the two E. coli is not identical. Consequently, our work shows persistence is a mechanism that bacteria could utilize to prevent their predation, and this persistence could be a potential answer for explaining E. coli E38???s resistance against bacterial predation. The difference in persistence tendencies between both E. coli strains suggests that the stress factor triggering this phenomenon and which evokes persistence in E. coli E38 is not clear and may be due to the numerous TA systems present within this bacterium, an idea that should be studied further.clos

CULTURAL INFLUENCE ON THE CHARACTERIZATIONS OF HEALTH BY KOREAN WOMEN LIVING IN THE UNITED STATES

The number of Korean migrants in the United States is continuously on the rise. As immigrants, they adapt to their new environment, including their understanding of health. This study explored the experience of Korean women living in the United States with respect to their perceptions of health and attempted to develop a substantive theory that explains the basic social process of adjusting to new life. Specifically, this study was undertaken to address the following questions: "How do Korean women living in the United States characterize health? and “To what extent does Korean and/or American culture affect such characterization?” This descriptive qualitative study utilized the grounded theory design. Accordingly, data collection comprised of purposive and theoretical sampling methods. In-depth, semi-structured, audio-taped interviews were conducted with a total of 20 Korean women in 20’s who have lived in the United States for at least two years. Interview data were transcribed verbatim and analyzed using Strauss and Corbin's constant comparative method. Findings indicated that Korean women use various methods of coping with new cultural environment and understanding toward health. Three main categories of health perceptions emerged: Physical health, mental and emotional health, and social health.Communication, Jack J. Valenti School o

The wound healing effect of four types of beta-glucan

Abstract Beta-glucans, which existed in the cell walls of cereals, bacteria, and fungi, comprise a group of β-d-glucose polysaccharides. We investigated the effects of four kinds of beta-glucan, that are derived from barley, yeast, mushroom, and euglena on wound healing. The migration and viability of keratinocyte or fibroblast were analyzed using the in vitro scratch wound healing assay, invasion assay, MTT assay, and in vivo assay. All the beta-glucans had a significant effect on keratinocyte migration at 20 μM and showed no toxicity on dermal fibroblast. Moreover, treatment of keratinocytes with the beta-glucan derived from the mushroom (Schizophyllum commune) promoted in vivo wound closure. The Integrin/FAK/Src pathway is known to affect cell migration by forming lamellipodia. Beta-glucan from S. commune activates the Integrin/FAK/Src signaling pathway in a time-dependent. Reactive oxygen species are associated with fibroblast differentiation to contract dermal layer and synthesize collagens. We found that fibroblast was activated by increasing NOX4 expression. We propose that beta-glucan derived from mushroom is capable of promoting keratinocyte migration via the induction of FAK/Src phosphorylation there by accelerating wound closure and activating dermal fibroblast differentiation through NADPH oxidase for matrix remodeling

Overcoming P-Glycoprotein-Mediated Multidrug Resistance in Colorectal Cancer: Potential Reversal Agents among Herbal Medicines

Objectives. Multidrug resistance (MDR) is the major reason for the failure of chemotherapy in colorectal cancer (CRC), and the primary determinant of MDR in CRC patients is active drug efflux owing to overexpression of P-glycoprotein (P-gp) in cancer tissues. Despite research efforts to overcome P-gp-mediated drug efflux, the high toxicity of P-gp inhibitors has been a major obstacle for the clinical use of these agents. The aim of this study was to review the literature for potential P-gp reversal agents among traditional herbal medicines, which offer the advantages of safety and potential synergetic effects in CRC chemotherapy. Methods. We searched ten databases including 3 English databases, 1 Chinese medical database, and 6 Korean medical databases up to July 2018 and included in vivo and in vitro studies evaluating the effects of herbal medicines as P-gp reversal agents in CRC. Results. A total of 28 potentially related studies were identified and 16 articles were included. Involving 3 studies about Salvia miltiorrhiza and 2 studies about Curcuma longa, finally we found 14 kinds of traditional herbal medicines—Salvia miltiorrhiza, Curcuma longa, Sinomenium acutum, Stephania tetrandra, Bufo gargarizans, Coptis japonica, Piper nigrum and Piper longum, Hedyotis diffusa, Schisandra chinensis, Glycyrrhiza glabra, Glycyrrhiza inflate, Daphne genkwa, Stemona tuberosa Lour, and Andrographis paniculata—as showing efficacy as P-gp inhibitors in anticancer drug-resistant CRC cells in vitro and in vivo. Conclusions. This brief account provides insight into the relationship between P-gp and CRC. Further studies on herbal medicines with demonstrated effects against P-gp overexpression will aid in improving the efficacy of chemotherapy in CRC

Viscosity has dichotomous effects on Bdellovibrio bacteriovorus HD100 predation

Bdellovibrio bacteriovorus HD100 is a highly motile predatory bacterium that consumes other Gram-negative bacteria for its sustenance. Here, we describe the impacts the media viscosity has both on the motility of predator and its attack rates. Experiments performed in polyethylene glycol (PEG) solutions, a linear polymer, found a viscosity of 10 mPa s (5% PEG) negatively impacted predation over a 24-h period. When the viscosity was increased to 27 mPa s (10% PEG), predation was nearly abolished. Tests with three other B. bacteriovorus strains, i.e., 109J and two natural isolates, found identical results. Short-term (2-h) experiments, however, found attack rates were improved in 1% PEG, which had a viscosity of 5.4 mPa s, using bioluminescent prey and their viabilities. In contrast, when experiments were performed in dextran, a branched polymer, no increase in predation was seen even though the viscosity was a comparable 5.1 mPa s. The enhanced attack rates in this solution coincided with a 31% increase in B. bacteriovorus HD100 swimming speeds (62 mu m s(-1) in 1% PEG vs. 47.5 mu m s(-1) in HEPES-salt)