Turning behaviors of T cells climbing up ramp-like structures are regulated by myosin light chain kinase activity and lamellipodia formation

T cells navigate diverse microenvironments to perform immune responses. Micro-scale topographical structures within the tissues, which may inherently exist in normal tissues or may be formed by inflammation or injury, can influence T cell migration, but how T cell migration is affected by such topographical structures have not been investigated. In this study, we fabricated ramp-like structures with a 5 mu m height and various slopes, and observed T cells climbing up the ramp-like structures. T cells encountering the ramp-like structures exhibited MLC accumulation near head-tail junctions contacting the ramp-like structures, and made turns to the direction perpendicular to the ramp-like structures. Pharmacological study revealed that lamellipodia formation mediated by arp2/3 and contractility regulated by myosin light chain kinase (MLCK) were responsible for the intriguing turning behavior of T cells climbing the ramp-like structures. Arp2/3 or MLCK inhibition substantially reduced probability of T cells climbing sharp-edged ramp-like structures, indicating intriguing turning behavior of T cells mediated by lamellipodia formation and MLCK activity may be important for T cells to access inflamed or injured tissues with abrupt topographical changes.11Ysciescopu

Common Sites, Etiology, and Solutions of Persistent Septal Deviation in Revision Septoplasty

Objectives To investigate the common causes of persistent septal deviation in revision septoplasty and to report the surgical techniques and results to correct them. Methods A total of 100 consecutive patients (86 males) who had revision septoplasty due to persistent septal deviation from 2008 and 2014 were included in the study. Their mean age was 35.6 years and the mean follow-up duration was 9.1 months. Presenting symptoms, sites of persistent septal deviation, techniques used to correct the deviation, and surgical results were reviewed. Results The mean interval between primary and revision surgery was 6.2 years. Forty-eight patients received revision septoplasty and 52 received revision septoplasty combined with rhinoplasty. Nasal obstruction was the most presenting symptom in almost all patients. The most common site of persistent septal deviation was middle septum (58%) followed by caudal septum (31%). Correcting techniques included further chondrotomy and excision of deviated portion in 76% and caudal batten graft in 39%. Rhinoscopic and endoscopic exams showed straight septum in 97% and 92 patients had subjective symptom improvement postoperatively. Conclusion Middle septum and caudal septum were common sites of persistent deviation. Proper chondrotomy with excision of deviated middle septum and correction of the caudal deviation with batten graft are key maneuvers to treat persistent deviation

Electro-acupuncture at acupoint ST36 reduces inflammation and regulates immune activity in Collagen-Induced Arthritic Mice

This study aimed to investigate the anti-inflammatory, anti-arthritic and immuno-regulatory effects of electro-acupuncture (EA) at ST36 on Collagen-induced arthritis (CIA) in mice. Male DBA/1J mice were divided into five groups: Normal, Control, NR (needle retention), EAI and EAII. All mice except those in the normal group were immunized with Collagen II for arthritis induction. Acupuncture needles were inserted into mice ST36 and electrical currents at a frequency of 2 Hz in a continuous rectangular wave form were conducted through the needles for 15 min, 3 times a week. EA treatments were administered for 5 weeks in the EAI group and for 9 weeks in the EAII group. The mice in the NR group were acupunctured in the same manner as the EA groups and the needles were retained for 15 min without electrical stimulation. CIA incidence analysis, ELISA, histological analysis and FACS analysis were performed to evaluate the effect of EA on CIA. EA at ST36 significantly reduced CIA incidence, IL-6, TNF-a, INF-γ, collagen II antibody, IgG and IgM levels in CIA mice serum and prevented knee joint destruction. EA at ST36 also reduced CD69+/CD3e+ cells and CD11a+/CD19+ cells in CIA mice lymph nodes, and CD11b+/Gr1+ cells in CIA mice knee joints. The ratios of CD3e+ cells to CD19+ cells, and CD8+ cells to CD4+ cells were maintained closer to the normal range in the EA groups as compared with the control group or the NR group. EAII was more effective than EAI throughout all the measurements. The NR was effective as well, though less effective than EA. EA at ST36 may have an anti-inflammatory, anti-arthritic and immuno-regulatory effects on CIA in mice. The effectiveness is stronger when EA starts earlier and is applied longer. Needle retention without electrical stimulation may be effective on CIA as well, however less effective than EA. Electrical stimulation and acupoint ST36 may have synergistic effects on CIA

MicroRNA-150 modulates intracellular Ca2+ levels in naïve CD8+ T cells by targeting TMEM20

Regulation of intracellular Ca2+ signaling is a major determinant of CD8+ T cell responsiveness, but the mechanisms underlying this regulation of Ca2+ levels, especially in naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in naïve CD8+ T cells required for activation by suppressing TMEM20, a negative regulator of Ca2+ extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca2+ levels in naïve CD8+ T cells. The subsequent increase in Ca2+ levels induced expression of anergy-inducing genes, such as Cbl-b, Egr2, and p27, through activation of NFAT1, as well as reduced cell proliferation, cytokine production, and the antitumor activity of CD8+ T cells upon antigenic stimulation. The anergy-promoting molecular milieu and function induced by miR-150 deficiency were rescued by reinstatement of miR-150. Additionally, knockdown of TMEM20 in miR-150-deficient naïve CD8+ T cells reduced intracellular Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in naïve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels115Ysciescopu

GarlicESTdb: an online database and mining tool for garlic EST sequences

<p>Abstract</p> <p>Background</p> <p><it>Allium sativum</it>., commonly known as garlic, is a species in the onion genus (<it>Allium</it>), which is a large and diverse one containing over 1,250 species. Its close relatives include chives, onion, leek and shallot. Garlic has been used throughout recorded history for culinary, medicinal use and health benefits. Currently, the interest in garlic is highly increasing due to nutritional and pharmaceutical value including high blood pressure and cholesterol, atherosclerosis and cancer. For all that, there are no comprehensive databases available for Expressed Sequence Tags(EST) of garlic for gene discovery and future efforts of genome annotation. That is why we developed a new garlic database and applications to enable comprehensive analysis of garlic gene expression.</p> <p>Description</p> <p>GarlicESTdb is an integrated database and mining tool for large-scale garlic (<it>Allium sativum</it>) EST sequencing. A total of 21,595 ESTs collected from an in-house cDNA library were used to construct the database. The analysis pipeline is an automated system written in JAVA and consists of the following components: automatic preprocessing of EST reads, assembly of raw sequences, annotation of the assembled sequences, storage of the analyzed information into MySQL databases, and graphic display of all processed data. A web application was implemented with the latest J2EE (Java 2 Platform Enterprise Edition) software technology (JSP/EJB/JavaServlet) for browsing and querying the database, for creation of dynamic web pages on the client side, and for mapping annotated enzymes to KEGG pathways, the AJAX framework was also used partially. The online resources, such as putative annotation, single nucleotide polymorphisms (SNP) and tandem repeat data sets, can be searched by text, explored on the website, searched using BLAST, and downloaded. To archive more significant BLAST results, a curation system was introduced with which biologists can easily edit best-hit annotation information for others to view. The GarlicESTdb web application is freely available at <url>http://garlicdb.kribb.re.kr</url>.</p> <p>Conclusion</p> <p>GarlicESTdb is the first incorporated online information database of EST sequences isolated from garlic that can be freely accessed and downloaded. It has many useful features for interactive mining of EST contigs and datasets from each library, including curation of annotated information, expression profiling, information retrieval, and summary of statistics of functional annotation. Consequently, the development of GarlicESTdb will provide a crucial contribution to biologists for data-mining and more efficient experimental studies.</p

Changes of hospitalization trend in the pediatric cardiology division of a single center by increasing adult with congenital heart disease

As a result of advances in pediatric care and diagnostic testing, there is a growing population of adults with congenital heart disease (ACHD). The purpose of this study was to better define the epidemiology and changes in the trend of hospitalizations for ACHD in Korean society. We reviewed outpatient and inpatient data from 2005 to 2017 to identify patient ≥18 years of age admitted for acute care with a congenital heart disease (CHD) diagnosis in the pediatric cardiology division. We tried to analyze changes of hospitalization trend for ACHD. The ratio of outpatients with ACHD increased 286.5%, from 11.1% (1748/15,682) in 2005 to 31.8% (7795/24,532) in 2017. The number of ACHD hospitalizations increased 360.7%, from 8.9% (37/414) in 2005 to 32.1% (226/705) in 2017. The average patient age increased from 24.3 years in 2005 to 27.4 in 2017. The main diagnosis for admission of ACHD is heart failure, arrhythmia and Fontan-related complications. The annual ICU admission percentage was around 5% and mean length of intensive care unit (ICU) stay was 8.4 ± 14.6 days. Mean personal hospital charges by admission of ACHD increased to around two times from 2005 to 2017. (from $2578.1 to$3697.0). Total annual hospital charges by ACHD markedly increased ten times (from $95,389.7 to$831,834.2). The number of hospital cares for ACHD dramatically increased more than five times from 2005 to 2017. We need preparations for efficient healthcare for adults with CHD such as a multi-dimensional approach, effective communication, and professional training

Clinical and Radiographic Features of Adult-onset Ankylosing Spondylitis in Korean Patients: Comparisons between Males and Females

The objective of this study was to investigate clinical and radiographic features and gender differences in Korean patients with adult-onset ankylosing spondylitis. Multicenter cross-sectional studies were conducted in the rheumatology clinics of 13 Korean tertiary referral hospitals. All patients had a confirmed diagnosis of ankylosing spondylitis according to the modified New York criteria. Clinical, laboratory, and radiographic features were evaluated and disease activities were assessed using the Bath ankylosing spondylitis disease activity index. Five hundred and five patients were recruited. The male to female ratio was 6.1:1. Average age at symptom onset was 25.4±8.9 yr and average disease duration was 9.6±6.8 yr. Males manifested symptoms at a significantly earlier age. HLA-B27 was more frequently positive in males. Hips were more commonly affected in males, and knees in females. When spinal mobility was measured using tragus-to-wall distance and the modified Schober's test, females had significantly better results. Radiographic spinal changes, including bamboo spine and syndesmophytes, were more common in males after adjustment of confounding factors. In conclusion, we observed significant gender differences in radiographic spinal involvement as well as other clinical manifestations among Korea patients with adult-onset ankylosing spondylitis. These findings may influence the timing of the diagnosis and the choice of treatment