• IMMUNE NETWORK
• /
• 제22권3호
• /
• pp.28.1-28.11
• /
• 2022

The 26S proteasome irreversibly hydrolyzes polyubiquitylated substrates to maintain protein homeostasis; it also regulates immune responses by generating antigenic peptides. An alternative form of the 26S proteasome is the immunoproteasome, which contains substituted catalytic subunits (β1i/PSMB9, β2i/PSMB10, and β5i/PSMB8) instead of constitutively expressed counterparts (β1/PSMB6, β2/PSMB7, and β5/PSMB5). The immunoproteasome expands the peptide repertoire presented on MHC class I molecules. However, how its activity changes in this context is largely elusive, possibly due to the lack of a standardized methodology to evaluate its specific activity. Here, we describe an assay protocol that measures the immunoproteasome activity of whole-cell lysates using commercially available fluorogenic peptide substrates. Our results showed that the most accurate assessment of immunoproteasome activity could be achieved by combining β5i-targeting substrate Ac-ANW-AMC and immunoproteasome inhibitor ONX-0914. This simple and reliable protocol may contribute to future studies of immunoproteasomes and their pathophysiological roles during viral infection, inflammation, and tumorigenesis.

• IMMUNE NETWORK
• /
• 제20권1호
• /
• pp.7.1-7.11
• /
• 2020

Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named "common factor" in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.

• 미생물학회지
• /
• 제22권1호
• /
• pp.19-28
• /
• 1984

A. conoides에 의한 선충 포획과정을 SEM과 TEM을 이용하여 관찰하였다. 1. A. conoides는 점착성 three-dimensional networks에 의해 선충을 포획한다. 2. Trap cell은 영양균사에 비해 세포벽이 두꺼우며 endoplasmic reticulum, mitochondria 및 electron-dense granule이 풍부하다. 3. 포획기관에서만 관찰되는 전자밀도가 높은 과립은 포획기관이 선충을 점착하여 침투하는 과정에서 소실된다. 4. 포획기관과 선충이 부착된 사이에서 osmiophilic layer가 관찰되었고 바로 이 지점으로부터 침투가 일어나며, 한 포획기관에서 두 군데 이상 동시 침투가 가능하다. 5. 포획기관의 선충내 침투시 appressorium이 형성되지 않고 침투되는 경우가 있다. 6. 균주와 선충의 혼합배지를 2~3주 두었을 때, 유충들이 포자에 접착되어 죽는다.

• Smart Structures and Systems
• /
• 제8권1호
• /
• pp.39-52
• /
• 2011

We are developing a biomimetic robot based on the Sea Lamprey. The robot consists of a cylindrical electronics bay propelled by an undulatory body axis. Shape memory alloy (SMA) actuators generate propagating flexion waves in five undulatory segments of a polyurethane strip. The behavior of the robot is controlled by an electronic nervous system (ENS) composed of networks of discrete-time map-based neurons and synapses that execute on a digital signal processing chip. Motor neuron action potentials gate power transistors that apply current to the SMA actuators. The ENS consists of a set of segmental central pattern generators (CPGs), modulated by layered command and coordinating neuron networks, that integrate input from exteroceptive sensors including a compass, accelerometers, inclinometers and a short baseline sonar array (SBA). The CPGs instantiate the 3-element hemi-segmental network model established from physiological studies. Anterior and posterior propagating pathways between CPGs mediate intersegmental coordination to generate flexion waves for forward and backward swimming. The command network mediates layered exteroceptive reflexes for homing, primary orientation, and impediment compensation. The SBA allows homing on a sonar beacon by indicating deviations in azimuth and inclination. Inclinometers actuate a bending segment between the hull and undulator to allow climb and dive. Accelerometers can distinguish collisions from impediment to allow compensatory reflexes. Modulatory commands mediate speed control and turning. A SBA communications interface is being developed to allow supervised reactive autonomy.

• BMB Reports
• /
• 제50권11호
• /
• pp.535-536
• /
• 2017

A novel approach has been used to identify functional interactions relevant to human disease. Using high-throughput human-yeast genetic interaction screens, a first draft of disease interactome was obtained. This was achieved by first searching for candidate human disease genes that confer toxicity in yeast, and second, identifying modulators of toxicity. This study found potentially disease-relevant interactions by analyzing the network of functional interactions and focusing on genes implicated in amyotrophic lateral sclerosis (ALS), for example. In the subsequent proof-of-concept study focused on ALS, similar functional relationships between a specific kinase and ALS-associated genes were observed in mammalian cells and zebrafish, supporting findings in human-yeast genetic interaction screens. Results of combined analyses highlighted MAP2K5 kinase as a potential therapeutic target in ALS.

• 전기학회논문지
• /
• 제66권1호
• /
• pp.137-143
• /
• 2017

In this paper, we investigate static control of Boolean networks described in the framework of semi-tensor product (STP) operation. The control objective is to determine control input nodes and their logical values so as to stabilize the considered Boolean network to a desired fixed point or cycle. Using topology of Boolean networks such as incidence matrix and hub nodes, a set of appropriate control input nodes is selected, and based on STP operations, we assign constant control inputs so that the controlled network can converge to a prescribed fixed point or cycle. To validate applicability of the proposed scheme, we conduct a numerical study on the problem of determining control input nodes for a Boolean network representing hierarchical differentiation of myeloid progenitors.

• Molecules and Cells
• /
• 제45권2호
• /
• pp.76-83
• /
• 2022

Neurons-on-a-Chip technology has been developed to provide diverse in vitro neuro-tools to study neuritogenesis, synaptogensis, axon guidance, and network dynamics. The two core enabling technologies are soft-lithography and microelectrode array technology. Soft lithography technology made it possible to fabricate microstamps and microfluidic channel devices with a simple replica molding method in a biological laboratory and innovatively reduced the turn-around time from assay design to chip fabrication, facilitating various experimental designs. To control nerve cell behaviors at the single cell level via chemical cues, surface biofunctionalization methods and micropatterning techniques were developed. Microelectrode chip technology, which provides a functional readout by measuring the electrophysiological signals from individual neurons, has become a popular platform to investigate neural information processing in networks. Due to these key advances, it is possible to study the relationship between the network structure and functions, and they have opened a new era of neurobiology and will become standard tools in the near future.

• 동의생리병리학회지
• /
• 제29권6호
• /
• pp.443-450
• /
• 2015

The purpose of this study was is to understand how the network pharmacology databases of traditional medicine in China are established and provide suggestion for successful implementation in Traditional Korean Medicine. We searched for network-pharmacology-related TCM Databases provided on the internet, and analysed their contents. Then, we compared herbs related to Sasang with herbs of the TCM Databases. We chose 8 network-pharmacology-related TCM Databases. They shared information about compounds, herbs, formulae, drugs, targets and diseases, and provided interaction networks between these components. In comparison with herbs related to Sasang, TCMSP Database did not have information about 99 herbs in total, and 25 herbs included in major Sasang formulae. The implications and recommendations for Traditional Korean Medicine researches were discussed. Based on the results of this primary study, more related studies should be carried out in the future.

• Reproductive and Developmental Biology
• /
• 제37권4호
• /
• pp.185-192
• /
• 2013

Many countries have implemented genetic evaluation for fertility traits in recent years. In particular, reproductive trait is a complex trait and need to require a system-level approach for identifying candidate genes related to the trait. To find the candidate gene associated with reproductive trait, we applied a weighted gene co-expression network analysis from expression value of bovine genes. We identified three co-expressed modules associated with reproductive trait from bovine microarray data. Hub genes (ZP4, FHL2 and EGR4) were determined in each module; they were topologically centered with statistically significant value in the gene co-expression network. We were able to find the highly co-expressed gene pairs with a correlation coefficient. Finally, the crucial functions of co-expressed modules were reported from functional enrichment analysis. We suggest that the network-based approach in livestock may an important method for analyzing the complex effects of candidate genes associated with economic traits like reproduction.

• Molecules and Cells
• /
• 제26권4호
• /
• pp.368-372
• /
• 2008

Recent molecular and genetic studies in rice, a short-day plant, have elucidated both conservation and divergence of photoperiod pathway genes and their regulators. However, the biological roles of rice genes that act within the autonomous pathway are still largely unknown. In order to better understand the function of the autonomous pathway genes in rice, we conducted molecular genetic analyses of OsFVE, a rice gene homologous to Arabidopsis FVE. OsFVE was found to be ubiquitously expressed in vegetative and reproductive organs. Overexpression of OsFVE could rescue the flowering time phenotype of the Arabidopsis fve mutants by up-regulating expression of the SUPPRESSOR OF OVEREXPRESSION OF CO1 (SOC1) and down-regulating FLOWERING LOCUS C (FLC) expression. These results suggest that there may be a conserved function between OsFVE and FVE in the control of flowering time. However, OsFVE overexpression in the fve mutants did not rescue the flowering time phenotype in in relation to the response to intermittent cold treatment.