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The aggressive nature and poor prognosis of lung cancer led us to explore the mechanisms driving disease progression. Utilizing our invasive cell-based model, we identified methylthioadenosine phosphorylase (MTAP) and confirmed its suppressive effects on tumorigenesis and metastasis. Patients with low MTAP expression display worse overall and progression-free survival. Mechanistically, accumulation of methylthioadenosine substrate in MTAP-deficient cells reduce the level of protein arginine methyltransferase 5 (PRMT5)-mediated symmetric dimethylarginine (sDMA) modification on proteins. We identify vimentin as a dimethyl-protein whose dimethylation levels drop in response to MTAP deficiency. The sDMA modification on vimentin reduces its protein abundance but trivially affects its filamentous structure. In MTAP-deficient cells, lower sDMA modification prevents ubiquitination-mediated vimentin degradation, thereby stabilizing vimentin and contributing to cell invasion. MTAP and PRMT5 negatively correlate with vimentin in lung cancer samples. Taken together, we propose a mechanism for metastasis involving vimentin post-translational regulation.

This study examines the means by which social actors at one largely Indigenous elementary school in Taiwan resolve the linguistic conflicts arising between official language policies and practical pedagogical practices. Special reference is made to Pangcah, an endangered indigenous language in contest with other languages, Mandarin inparticular, as the medium of instruction. The findings highlight the use of code-switches between languages in the context of the lesson being observed. The "depreciation" of the Pangcah language can be understood as reflective of enduring symbolic and hegemonic dominations, the instability of the indigenous language being a manifestation of Pangcah's limited social status. While teachers may vociferously advocate Pangcah as a means of identity construction, they remain committed to Mandarin. It is suggested that their commitment to Mandarin reveals an internalization of the majority ideology that sees Mandarin as the most advantageous means by which indigenous children can adapt to the larger Sino-cultural social mainstream.

This study examines incongruent languages ideologies as they exist among parents, grandparents and community members of Taiwan's aboriginal Pangcah people. The language ideologies of the villagers function as language policy that informs their decisions in favor of transmitting or abandoning their linguistic heritage. Taking a critical perspective on the study of language maintenance and shift, an ethnographic/discourse analytic approach to language ideologies is applied. The main insight gained from this study of ideological contention is that there are various language ideologies indexing speakers' linguistic value. Within the ideologies of valuing and devaluing, Pangcah incorporates the hybridity of stigmatized and assimilated identities under the macrohistorical colonial processes. As a response to increasing economic pressure, the Pangcah identity with language and culture have shifted to the state and dominant languages of Mandarin and Southern Min. Consequently, efforts to maintain and learn Pangcah have diminished, making the ideology of valuing the dominant code correspondingly more successful and common. (Contains 13 notes.)

Background Chronic kidney disease (CKD) is pathologically correlated with a sophisticated milieu of innate and adaptive immune dysregulation, but the underlying immunological disturbances remain poorly understood. Methods To address this, we comprehensively interrogated cellular and soluble elements of the immune system by using high-dimensional flow cytometry to analyze peripheral blood mononuclear cells and performing cytokine/chemokine profiling of serum samples, respectively, in a cohort of 69 patients and 19 non-CKD controls. Results Altered serum levels of several cytokines/chemokines were identified, among which concentrations of stem cell factor (SCF) were found to be elevated with the progression of CKD and inversely correlated with estimated glomerular filtration rate (eGFR). Deep immunophenotyping analyses reveal a global change in immune modulation associated with CKD severity. Specifically, a decrease in the subsets of CD56dim natural killer (NK) cells (KLRG-1+CD38+CD64+CD15+CD197+) and monocytes (KLRG-1+CD38+PD-1+) was detected in severe CKD compared with controls and mild CKD. In addition, comparisons between mild and severe CKD demonstrated a loss of a mature B cell population (PD-1+CD197+IgD+HLA-DR+) in the advanced stages of disease. Further, we identified immunophenotypic markers to discriminate mild CKD from the controls, among which the portion of CD38+ monocytes was of particular value in early diagnosis. Conclusions Our data unveil severity-specific immunological signatures perturbed in CKD patients. [ABSTRACT FROM AUTHOR]