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BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation and cartilage/bone damage. Intercellular messengers such as IL-1 and TNF play a crucial role in the pathophysiology of RA but have limited diagnostic and prognostic values. Therefore, we assessed whether the protein content of the recently discovered extracellular vesicles (EVs), which have gained attention in the pathogenesis of RA, correlates with disease activity parameters in RA patients.MethodsWe identified and quantified proteins in plasma-derived EVs (pEVs), isolated by size exclusion chromatography from 17 RA patients by mass spectrophotometry (MS). Quantified protein levels were correlated with laboratory and clinical parameters and the patient’s own global assessment of their disease activity (PGA-VAS). In a second MS run, the pEV proteins of nine other RA patients were quantified and compared to those from nine healthy controls (HC).ResultsNo differences were observed in the concentration, size, and protein content of pEVs from RA patients. Proteomics revealed >95% overlapping proteins in RA-pEVs, compared to HC-pEVs (data are available via ProteomeXchange with identifier PXD046058). Remarkably, in both runs, the level of far more RA-pEV proteins correlated positively to PGA-VAS than to either clinical or laboratory parameters. Interestingly, all observed PGA-VAS positively correlated RA-pEV proteins were associated with the actin-cytoskeleton linker proteins, ezrin, and moesin.ConclusionOur observation suggests that PGA-VAS (loss of vitality) may have a different underlying pathological mechanism in RA, possibly related to enhanced muscle actin-cytoskeleton activity. Furthermore, our study contributes to the growing awareness and evidence that pEVs contain valuable biomarkers for diseases, with added value for RA patients.

Learning is more concerned in engineering education as students need to do deep learning to understand the engineering principles for practice. Engineering is a practicing profession. Therefore, providing learning environment is required for the subjects of engineering disciplines to enable students to learn in depth. By knowing this phenomenon, field study was conducted as a group study for the civil engineering subject of building construction allowing students to learn and gain knowledge by observing construction activities in construction projects in addition to the lectures in usual classroom. At the end of the study, it is found that field study is useful for learning and students acquire knowledge and understand the application of theory at real situation. In addition, students develop skills for working as a team by organizing their works, sharing knowledge, discussing with relevant technical personnel at work site and achieving the targets within the given time frame. It is realized that teacher's role is vital to make the study successful in the ways of organizing field study, conducting discussion classes to assist students, monitoring the progress and giving the feedback of the students' performance during the course of field study producing excellent results while satisfying the objectives of both teacher and students.

Teaching is to be amalgamated with learning environment where students attend work with interest. Coursework was designed and conducted for Quantity Surveying module from 2014 as a study and found that it has supported for promoting teaching and learning. It was revealed that encouragement made only for attendance is not sufficient to obtain high performance. With developed coursework in 2016, students have obtained high marks for yearend paper reaching to grades A and B by 35% and 46% respectively. In addition, more than 82% of students have expressed that the method conducted was at good level. High impact obtained in 2015 and 2016 may be due to the experience gathered by the teacher in implementing this method continuously and therefore this coursework benefited not only to the students but also to the teachers as both parties are able to achieve their objectives with high performances.

Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s). Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s) or healthy and disease controls. Podocyte proteomes were analyzed by LC–MS. Results were validated using flow cytometry, RT-PCR, and immunofluorescence. Podocyte granularity was examined using flow cytometry, electron microscopy imaging, and BODIPY staining. Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, and correlated with the capacity of plasma to induce podocyte granularity, identified as lipid droplet accumulation. Elevated podocyte perilipin-2 was confirmed at protein and mRNA level and was also detected in glomeruli of FSGS patients whose active disease plasmas induced podocyte perilipin-2 and lipid droplets. Our study demonstrates that presumably, CPF-containing plasmas from FSGS patients induce podocyte lipid droplet accumulation and perilipin-2 expression, identifying perilipin-2 as a potential biomarker. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism, which ultimately may result in novel leads for treatment.

Polycomb Repressive Complex 2 (PRC2) plays critical roles in transcriptional silencing during development. Here the authors identify EZHIP as a cofactor of PRC2 expressed predominantly in the gonads, finding that EZHIP limits the enzymatic activity of PRC2 in germ cells in mice.

The NuRD complex plays an important role in regulating lineage commitment and cell fate during early embryonic development. Here the authors present an integrative analysis of MBD3/NuRD composition and binding in mouse embryonic stem cells and neural progenitor cells, providing a molecular basis for genome-wide NuRD localization

Detecting proteins and post-translational modifications is important for drug screens, but the number of proteins measurable simultaneously is limited. Here the authors use antibodies tagged with DNA barcodes and high-throughput sequencing to detect up to 70 (phospho-)proteins in stem cells.

Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

Nature Communications 8: Article number: 15034 (2017); Published: 27 May 2017; Updated: 5 March 2018 The original version of this Article contained an error in the spelling of two members of the GenoMEL Consortium, Joan Anton Puig-Butille and Pol Gimenez-Xavier, which were incorrectly given as Joan-Anton Puig Butille and Pol Gimenez Xavier respectively.

Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s). Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s) or healthy and disease controls. Podocyte proteomes were analyzed by LC–MS. Results were validated using flow cytometry, RT-PCR, and immunofluorescence. Podocyte granularity was examined using flow cytometry, electron microscopy imaging, and BODIPY staining. Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, and correlated with the capacity of plasma to induce podocyte granularity, identified as lipid droplet accumulation. Elevated podocyte perilipin-2 was confirmed at protein and mRNA level and was also detected in glomeruli of FSGS patients whose active disease plasmas induced podocyte perilipin-2 and lipid droplets. Our study demonstrates that presumably, CPF-containing plasmas from FSGS patients induce podocyte lipid droplet accumulation and perilipin-2 expression, identifying perilipin-2 as a potential biomarker. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism, which ultimately may result in novel leads for treatment. [ABSTRACT FROM AUTHOR]