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Vomeronasal organ (VNO) is a tubular pheromone sensing organ in which the lumen is covered with sensory and non-sensory epithelia. This study used immunohistochemistry and lectin histochemistry techniques to evaluate developmental changes, specifically of the glycoconjugate profile, in the horse VNO epithelium. Immunostaining analysis revealed PGP9.5 expression in some vomeronasal non-sensory epithelium (VNSE) cells and in the vomeronasal receptor cells of the vomeronasal sensory epithelium (VSE) in fetuses, young foals, and adult horses. OMP expression was exclusively localized in receptor cells of the VSE in fetuses, young foals, and adult horses and absent in VNSE. To identify the glycoconjugate type, lectin histochemistry was performed using 21 lectins. Semi-quantitative analysis revealed that the intensities of glycoconjugates labeled with WGA, DSL, LEL, and RCA120 were significantly higher in adult horse VSE than those in foal VSE, whereas the intensities of glycoconjugates labeled with LCA and PSA were significantly lower in adult horse VSE. The intensities of glycoconjugates labeled with s-WGA, WGA, BSL-II, DSL, LEL, STL, ConA, LCA, PSA, DBA, SBA, SJA, RCA120, jacalin, and ECL were significantly higher in adult horse VNSE than those in foal VNSE, whereas the intensity of glycoconjugates labeled with UEA-I was lower in adult horse VNSE. Histochemical analysis of each lectin revealed that various glycoconjugates in the VSE were present in the receptor, supporting, and basal cells of foal and adult horses. A similar pattern of lectin histochemistry was also observed in the VNSE of foal and adult horses. In conclusion, these results suggest that there are increase in the level of N-acetylglucosamine (labeled by WGA, DSL, LEL) and galactose (labeled by RCA120) in horse VSE during postnatal development, implying that they may influence the function of VNO in adult horses.

Extracellular vesicles (EVs) are membranous vesicles that are released by both prokaryotic and eukaryotic cells into the extracellular microenvironment. EVs can be categorised as exosomes, ectosomes or shedding microvesicles and apoptotic bodies based on the mode of biogenesis. EVs contain biologically active cargo of nucleic acids, proteins, lipids and metabolites that can be altered based on the precise state of the cell. Vesiclepedia (http://www.microvesicles.org) is a web-based compendium of RNA, proteins, lipids and metabolites that are identified in EVs from both published and unpublished studies. Currently, Vesiclepedia contains data obtained from 1254 EV studies, 38 146 RNA entries, 349 988 protein entries and 639 lipid/metabolite entries. Vesiclepedia is publicly available and allows users to query and download EV cargo based on different search criteria. The mode of EV isolation and characterization, the biophysical and molecular properties and EV-METRIC are listed in the database aiding biomedical scientists in assessing the quality of the EV preparation and the corresponding data obtained. In addition, FunRich-based Vesiclepedia plugin is incorporated aiding users in data analysis.

Although ACE2 is the primary receptor for SARS-CoV-2 infection, a systematic assessment of host factors that regulate binding to SARS-CoV-2 spike protein has not been described. Here we use whole genome CRISPR activation to identify host factors controlling cellular interactions with SARS-CoV-2. Our top hit was aTLR-related cell surface receptor calledleucine-rich repeat-containing protein 15(LRRC15).LRRC15expression was sufficient to promote SARS-CoV-2 Spike binding where they form a cell surface complex.LRRC15mRNA is expressed in human collagen-producing lung myofibroblasts and LRRC15 protein is induced in severe COVID-19 infection where it can be found lining the airways. Mechanistically, LRRC15 does not itself support SARS-CoV-2 infection, but fibroblasts expressing LRRC15 can suppress both pseudotyped and authentic SARS-CoV-2 infection intrans. Moreover, LRRC15 expression in fibroblasts suppresses collagen production and promotes expression of IFIT, OAS, and MX-family antiviral factors. Overall, LRRC15 is a novel SARS-CoV-2 spike-binding receptor that can help control viral load and regulate antiviral and antifibrotic transcriptional programs in the context of COVID-19 infection.

Proteases are enzymes that regulate substrates via proteolytic activation and coordinate essential cellular functions including DNA replication, DNA transcription, cell proliferation, differentiation, migration and apoptosis. However, techniques to identify proteolytic events in a high-throughput manner is limited. PROtein TOpography and Migration Analysis Platform (PROTOMAP) is a technique that relies on mass spectrometry-based proteomics to globally identify the shifts in the in-gel migration of proteins and their corresponding fragments that are obtained by proteolysis. However, user-friendly software tool to analyse the proteomic data to identify proteolytic events is needed. Here, we report Pep2Graph, a user-friendly standalone tool that integrates peptide sequence information from in-gel proteomics and presents the data as two-dimensional peptographs with in-gel migration, sequence coverage and MS/MS spectra counts. Pep2Graph (http://www.mathivananlab.org/Pep2Graph) allows users to utilize in-gel proteomics data to study proteolytic events that may play a significant role in normal physiology and pathology.

Extracellular vesicles (EVs) refer to vesicles that are released by cells into the extracellular space. EVs mediate cell-to-cell communication via delivery of functional biomolecules between host and recipient cells. EVs can be categorised based on their mode of biogenesis and secretion and include apoptotic bodies, ectosomes or shedding microvesicles and exosomes among others. EVs have gained immense interest in recent years owing to their implications in pathophysiological conditions. Indeed, EVs have been proven useful in clinical applications as potential drug delivery vehicles and as source of diagnostic biomarkers. Despite the growing body of evidence supporting the clinical benefits, the processes involved in the biogenesis of EVs are poorly understood. Hence, it is critical to gain a deeper understanding of the underlying molecular machineries that ultimately govern the biogenesis and secretion of EVs. This chapter discusses the current knowledge on molecular mechanisms involved in the biogenesis of various subtypes of EVs.

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Hence, it is crucial to explore new therapeutic avenues to sensitise NBL. Recently, bovine milk-derived extracellular vesicles (MEVs) have been proposed to contain anti-cancer properties. However, the impact of MEVs on NBL cells is not understood. In this study, we characterised MEVs using Western blotting, NTA and TEM. Importantly, treatment of NBL cells with MEVs decreased the proliferation and increased the sensitivity of NBL cells to doxorubicin. Temporal label-free quantitative proteomics of NBL cells highlighted the depletion of proteins involved in cell metabolism, cell growth and Wnt signalling upon treatment with MEVs. Furthermore, proteins implicated in cellular senescence and apoptosis were enriched in NBL cells treated with MEVs. For the first time, this study highlights the temporal proteomic profile that occurs in cancer cells upon MEVs treatment.

Neuroblastoma (NBL) is a pediatric cancer that accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc occurs in 20% of NBL patients and is considered high risk as it correlates with aggressiveness, treatment resistance and poor prognosis. Even though the treatment strategies have improved in the recent years, the survival rate of high-risk NBL patients remain poor. Hence, it is crucial to explore new therapeutic avenues to sensitise NBL. Recently, bovine milk-derived extracellular vesicles (MEVs) have been proposed to contain anti-cancer properties. However, the impact of MEVs on NBL cells is not understood. In this study, we characterised MEVs using Western blotting, NTA and TEM. Importantly, treatment of NBL cells with MEVs decreased the proliferation and increased the sensitivity of NBL cells to doxorubicin. Temporal label-free quantitative proteomics of NBL cells highlighted the depletion of proteins involved in cell metabolism, cell growth and Wnt signalling upon treatment with MEVs. Furthermore, proteins implicated in cellular senescence and apoptosis were enriched in NBL cells treated with MEVs. For the first time, this study highlights the temporal proteomic profile that occurs in cancer cells upon MEVs treatment.

The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors., Dietary extracellular vesicles (EVs) could potentially be absorbed by the intestinal tract of the host and exert multiple phenotypic changes. Here, the authors isolate and characterize EVs from raw and commercial bovine milk and show orally administered EVs to have a context specific role in promoting or suppressing primary tumor growth and metastasis in multiple mouse tumor models.

Extracellular vesicles (EVs) refer to vesicles that are released by cells into the extracellular space. EVs mediate cell-to-cell communication via delivery of functional biomolecules between host and recipient cells. EVs can be categorised based on their mode of biogenesis and secretion and include apoptotic bodies, ectosomes or shedding microvesicles and exosomes among others. EVs have gained immense interest in recent years owing to their implications in pathophysiological conditions. Indeed, EVs have been proven useful in clinical applications as potential drug delivery vehicles and as source of diagnostic biomarkers. Despite the growing body of evidence supporting the clinical benefits, the processes involved in the biogenesis of EVs are poorly understood. Hence, it is critical to gain a deeper understanding of the underlying molecular machineries that ultimately govern the biogenesis and secretion of EVs. This chapter discusses the current knowledge on molecular mechanisms involved in the biogenesis of various subtypes of EVs.

The aim of the study was to examine the usefulness of targeted musculoskeletal ultrasonography (MSUS) in assessing the disease activity of patients with early inflammatory arthritis (EIA). Twenty-eight patients with EIA were enrolled. The MSUS examination of joints with arthritic signs (tenderness or swelling), measurement of 28-joint Disease Activity Score (DAS28), and its components were performed at four-week interval visits until power doppler (PD) US remission was achieved. Various MSUS parameters of grey scale (GS) and PD synovitis were measured. Pearson or Spearman correlation coefficients were determined for the purpose of the study. Data were gathered from a total of 85 visits. The Sum of GS grade correlated better with physical examination findings, while the Sum of PD grade correlated better with serum inflammatory markers and patient global health. However, Global OMERACT-EULAR Synovitis Score (GLOESS), which reflected both PD and GS grades, correlated evenly well with each clinical parameter. In addition, GLOESS correlated best with DAS28 in the overall study population (p &lt, 0.01). Conclusively, our targeted MSUS parameters of arthritic joints, especially sums of semi-quantitative grades of synovitis, could be useful in monitoring patients with EIA.

High-throughput methods to profile the genome, transcriptome, proteome and metabolome of various systems has become a routine in multiple research laboratories around the world. Hence, to analyse and interpret these heterogenous datasets user-friendly bioinformatics tools are needed. Here, we discuss FunRich tool that enables biologists to perform functional enrichment analysis on the generated datasets. Users can perform enrichment analysis with a variety of background databases and have complete control in updating or modifying the content in most of the databases. Specifically, users can download and update the background database from UniProt at any time thereby allowing a robust background database that can support annotations from >18 taxonomies. Users can create customizable Venn diagrams, pie charts, bar graphs and heatmaps of publication quality for their datasets using FunRich (http://www.funrich.org). Overall, FunRich tool is user-friendly and enables users to perform various analysis on their datasets with minimal or no aid from bioinformaticians.

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation of the large intestine, rectal bleeding, and abdominal pain. It can be alleviated by certain bioactive compounds, including α-linolenic acid (ALA), which is a bioactive component in fermented black radish (Raphanus sativus L. var. niger). The aim of this study was to evaluate the anti-inflammatory effects of ALA in dextran sulfate sodium (DSS)-induced UC in mice. UC was induced in C57BL/6 mice by allowing them to freely drink water containing 2.5% DSS for 7 days, followed by oral administration of ALA (30 and 60 mg/kg/day) or vehicle control for 7 days. DSS-induced colitis was evaluated using the Disease Activity Index (DAI) and by measuring colon length and performing a histopathological examination. Compared to the control group, the vehicle-treated group showed a higher DAI score, shorter colon, goblet cell loss, and crypt shortening. The ALA treatment mitigated clinical signs of UC and histopathological changes. Furthermore, it mitigated intestinal inflammation by reducing the expression of ionized calcium binding adaptor molecule 1-positive macrophages in the colon. These results show that ALA alleviates DSS-induced UC by suppressing colon damage, which includes goblet cell loss, crypt shortening, and a reduction of macrophages in the colon.

In this study, surface-enhanced Raman scattering (SERS) scheme is combined with localized surface plasmon resonance (LSPR) detection on a thin gold film with stripe patterns of gold nanoparticles (GNPs) via convective self-assembly (CSA) method. The potential of dual modal plasmonic substrates was evaluated by binding 4-ABT and IgG analytes, respectively. SERS experiments presented not only a high sensitivity with a detection limit of 4.7 nM and an enhancement factor of 1.34 × 105, but an excellent reproducibility with relative standard deviation of 5.5%. It was found from plasmonic sensing experiments by immobilizing IgG onto GNP-mediated gold film that detection sensitivity was improved by more than 211%, compared with a conventional bare gold film. Our synergistic SERS–LSPR approach based on a simple and cost-effective CSA method could open a route for sensitive, reliable and reproducible dual modal detection to expand the application areas.

Musculoskeletal ultrasound is a powerful tool not only for evaluating joint and related structures but also for assessing disease activity. Ultrasound in rheumatology has rapidly evolved and been incorporated into routine clinical practice over the past decade. Moreover, technological development of equipment has made it more accessible for rheumatologists. We present a review of advances in ultrasound in rheumatology, focusing on major chronological developments.

Rheumatoid arthritis (RA) is frequently associated with various extra-joint complications. Although rare, thromboembolic complications are associated with high morbidity and mortality. We experienced a very rare case of nonbacterial thrombotic endocarditis (NBTE) and subsequent embolic stroke in a patient with RA. A 72-year-old male with a 15-year history of RA suddenly developed neurologic symptoms of vomiting and dizziness. Brain magnetic resonance imaging revealed recently developed multiple cerebellar and cerebral lacunar infarctions. Echocardiography showed a pulsating mitral valve vegetation involving the posterior cusp of the mitral valve leaflet, which was confirmed as NBTE. Immediate anti-coagulation therapy was started. The NBTE lesion disappeared in follow-up echocardiography after 4 weeks of anti-coagulation treatment.

In this study, we designed microscope for real-time observation of the cells. This microscope uses a smartphone as detector. Therefore, we can observe in real time cells through the remote control of smartphone

Aim In collaboration with the Targeted Ultrasound Initiative (TUI), to conduct the first study in Korea to investigate current practices in ultrasound use among Korean rheumatologists. Methods We translated the TUI Global Survey into Korean and added questions to better understand the specific challenges facing rheumatologists in Korea. To target as many rheumatologists in Korea as possible, we created an on-line version of this survey, which was conducted from March to April 2013. Results Rheumatologists are in charge of ultrasound in many Korean hospitals. Rheumatologists in hospitals and private clinics use ultrasound to examine between one and five patients daily; they use ultrasound for diagnosis more than monitoring and receive compensation of about US$30–50 per patient. There are marked differences in the rates of ultrasound usage between rheumatologists who work in private practice compared with tertiary hospitals. Korean rheumatologists not currently using ultrasound in their practice appear eager to do so. Conclusion This survey provides important insights into the current status of ultrasound in rheumatology in Korea and highlights several priorities; specifically, greater provision of formal training, standardization of reporting and accrual of greater experience among ultrasound users. If these needs are addressed, all rheumatology departments in Korea are likely to use ultrasound or have access to it in the future.

Fibrotic involvement of the skin is a cardinal feature of systemic sclerosis (SSc). The extent of skin involvement is associated with internal organ involvement, coinciding with more severe disease course and poor prognosis. A palpation-based semi-quantitative score, the modified Rodnan skin score, is widely used for the assessment of skin involvement, but it is entailed by significant limitations. More objective approaches to measure skin involvement employing imaging have been explored continuously in the past decades and are currently advancing. Here, we review the use of different imaging techniques for the assessment of skin involvement in patients with SSc, focusing mainly on ultrasound, magnetic resonance imaging, and optical coherence tomography.

Ultrasound is gradually becoming established as an indispensable tool within the rheumatology clinical setting. Falling costs, improved educational opportunities, standardisation and developments in therapeutics have all led to the greater acceptability of the technique. This review will highlight how far ultrasound has come in a relatively short period of time by providing an overview of how it is being applied in rheumatology today.

The use of musculoskeletal ultrasound in rheumatology clinical practice has rapidly increased over the past decade. Ultrasound has enabled rheumatologists to diagnose, prognosticate and monitor disease outcome. Although international standardization remains a concern still, the use of ultrasound in rheumatology is expected to grow further as costs fall and the opportunity to train in the technique improves. We present a review of value of ultrasound, focusing on major applications of ultrasound in rheumatologic diseases.

In this study, we conducted a genome-wide linkage analysis to identify the quantitative trait loci (QTL) that influence back fat thickness and carcass pH in an F(2) intercross between Landrace and Korean native pigs. Eight phenotypes related with back fat thickness and carcass pH were measured in more than 960 F(2) progeny. All experimental animals were subjected to genotypic analysis using 173 microsatellite markers located throughout the pig genome. The GridQTL program, based on the least squares regression model, was used to perform the QTL analysis. We identified 22 genome-wide significant QTL in 9 chromosomal regions (SSC1, 2, 5, 6, 7, 8, 12, 15, and 16) and 29 suggestive QTL in 16 chromosomal regions (SSC2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 14, 15, 16, 17, 18, and X). On SSC5, we detected a QTL affecting back fat thickness that accounted for 4.8 % of the phenotypic variance, which was the highest test statistic (F-ratio = 50.3 under the additive model, nominal P value = 2.5 × 10(-12)) observed in this study. Additionally, we showed that there were significant QTL on SSC16 affecting carcass pH traits. In conclusion, the QTL identified in this study together with associated positional candidate genes could play an important role in determining the genetic structure underlying the variation of back fat thickness and carcass pH in pigs.

pISSN: 2093-940X, eISSN: 2233-4718 Copyright c 2016 by The Korean College of Rheumatology. All rights reserved. This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited. Review Article Journal of Rheumatic Diseases Vol. 23, No. 1, February, 2016 http://dx.doi.org/10.4078/jrd.2016.23.1.11

Retroperitoneal fibrosis (RPF) is a rare, progressive disease characterized by chronic non specific inflammation of the retroperitoneum. Although the pathogenesis of idiopathic retroperitoneal fibrosis (IRF) remains unclear, IRF has been reported in association with autoimmune disorders. However, few cases of IRF associated with rheumatoid arthritis (RA) have been reported. We experienced a rare case of IRF in a patient with RA and chronic B viral hepatitis. A 39-year-old Korean man with RA and hepatitis B was referred to our hospital due to left hydronephrosis. An abdominal computed tomography (CT) scan and magnetic resonance imaging (MRI) showed a diffuse infiltrating retroperitoneal mass around the abdominal aorta and left ureter. The patient underwent intraureteral stent insertion and was treated with corticosteroid. Three months later, the follow up abdominal CT showed that the retroperitoneal mass had decreased in size. Herein, we report the first case of coexistent IRF, RA, and chronic B viral hepatitis with a literature review. (J Rheum Dis 2015;22:123-126)

We describe a 48-year-old man with family history of rheumatoid arthritis (RA) affected by chronic eosinophilic pneumonia (CEP) with severe peripheral eosinophilia. CEP might develop as a complication of longstanding active RA. The patient with 5 months history of seropositive RA and chronic respiratory symptoms, alveolar and blood eosinophilia, peripheral pulmonary infiltrates and pleural effusion on chest imaging. The lung may be involved as an extraarticular manifestation of RA. However, CEP is not recognized as a typical lung manifestation of RA, and the two diseases rarely coexist. The effusion was an eosinophil predominant exudates and was characterized by low pH, and glucose level and high lactic dehydrogenase. The patient responded rapidly to combination of steroids and disease modifying anti-rheumatic drugs.

Rhabdomyolysis is caused by injury to skeletal muscle and it involves leakage of intracellular contents into the plas- ma. Rhabdomyolysis is an extremely rare manifestation of dermatomyositis. Dermatomyositis is a rare idiopathic in- flammatory myopathy that is characterized by chronic in- flammation of skeletal muscles and skin, resulting in mus- cle weakness. A 20 year old Korean male soldier presented with acute muscle pain, weakness and skin rashes over the face, neck and anterior chest. He received military train- ing with carrying a radio set one week previouslyago. The patient was treated for rhabdomyolysis. However, the pa- tient's symptoms did not improve. Muscle biopsy results suggested the diagnosis of rhabdomyolysis. Nevertheless, the features of skin and muscle inflammation raised the possibility of dermatomyositis. High dose steroid treatment was started, and then the symptoms and signs of muscle inflammation were improved. Rhabdomyolysis as the pre- senting sign of dermatomyositis has not been reported in Korea. Thus, we report on this case with a literature review.

환 자: 78세 남자 주 소: 한 달 전부터 시작된 양측 손등의 다발성 결절 및 농포를 동반한 부종 병 력: 담낭 절제술을 시행받은 과거력 있으며, 간헐성 심방 세동과 전립선 비대증으로 약물 복용 중 이었고, 3년 전 류마티스관절염을 진단받은 후 경구 트리암시놀론(triamcinolone) 4 mg/day와 methotrexate 7.5 mg/week를 복용 중이었다. 이학적 소견: 양측 손등에 특징적인 작은 결절들 과 농포가 관찰되었고 전반적인 부종 소견을 보였 다. 유동성 피하농과 함께 농포에서 화농성 분비물 이 관찰되었다(그림 1). 검사실 소견: 혈액검사에서 혈색소 10.4 g/dL, 혈 소판 118,000/mm이었고 전해질 검사상 특이 소견 없 었으며 적혈구침강속도 2 mm/h, C 반응성 단백 1.21 mg/dL이었다. 농포에서 채취한 화농성 분비물을 배 양한 결과 비교적 두꺼운 세포벽을 가진 균사와 균 사의 끝이나 측면에서 자라나는 분생자병(conidophore), 분생자병 끝에 형성된 난원형(ovoid shape)의 단일 분생자(single conidium)가 관찰되어 Scedosporium apiospermum의 피부 감염으로 진단하였다(그림 2). 치료 및 경과: 농포에 대하여 절개 및 배농을 시 행 하였으며 경험적으로 항생제를 사용하던 중 배양 결과가 보고되어, 이후 itraconazole 400 mg/day을 2 주간 경구 투여한 후에 병변은 호전되었다.