The Rhetorical Discourse Revealing The Indonesians Characters

Indonesia comprises of many tribes and language spreading all over its islands from Sabang to Merauki. The tribes and their languages are unique symbolizing that they are heterogeneous society who live in a place named Indonesia. They live in harmony and they are happy being Indonesians. This can happen because they have one motto unity in diversity (Bhinneka Tunggal Ika) and a sacred symbol of five principles Pancasila. The symbol of Pancasila and a motto unity in diversity motivate the world to see the unique and harmonious country and its people. What are the real characters of Indonesian and how they are represented in the rhetorical discourse presented by formal speech of president of Indonesia, Mr. Joko Widodo in delivering speech on Pancasila Day 1 June 2017. This article wants to elaborates the characters of Indonesians and the way they are presented in the discourse. This article uses critical discourse of analysis and systemic functional linguistic. This article uses critical discourse analysis and the systemic functional linguistic because the discourse being release is not appearing without any sense. There is a background which escorting the releasing of this discourse. This article finds out that Indonesians have to return to their real original characteristic, such as gotong Royong (supporting each other), Bhinneka Tunggal Ika (unity and diversity) and toleransi (tolerance). They are folded within Pancasila (five principles). Theseidentifications of characteristic are released because the values of Pancasila have been neglected by many group of people after reformation era. As examples are the tolerance is decreasing, the unity in diversity has been disturbed by the existence of other ideology in which it is contradictory to Pancasila. This article found out that there are thre domain idenification of the Indonesian peole that shuld be reestablished. They are supporting each other, unity in diversity and the tolence. They become the pride of the Indonesians and they become the examplary nation which applies the high tolerance among its people. The depicted identifications are clearly stated in the official speech presented by President Joko Widodo in the celebration of Pancasila day 2017. Key words: supporting each other, tolerance, unity and diversity, discourse

Therapeutic approaches to enhance PINK1/Parkin mediated mitophagy for the treatment of Parkinson's disease

The discovery of rare familial monogenic forms of early-onset Parkinson's disease has led to the identification of a mitochondrial quality control process as a key player in this disease. Loss-of-function mutations in the genes encoding PINK1 or Parkin result in insufficient removal of dysfunctional mitochondria through autophagy, a process termed mitophagy. Understanding the mechanism of this process and the function of its two key players, PINK1 and Parkin, has led to the discovery of new therapeutic approaches. Small molecule activators of mitophagy, either activating PINK1 or Parkin directly or inhibiting Parkin's counterplayer, the ubiquitin-specific protease USP30, are in preclinical development. To enable clinical success of future small molecule mitophagy enhancers, biomarkers for mitochondrial integrity and mitophagy are being developed. Only a few years after the discovery of mitophagy deficits in Parkinson's disease, research of the underlying mechanisms, drug discovery of modulators for this mechanism and identification of biomarkers provide new avenues towards the development of disease-modifying therapies.</p

The novel MAPT mutation K298E:mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons

Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30 % of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with FTDP-17T. Neuropathological studies of post-mortem brain showed widespread neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in neurons and glia. Molecular studies demonstrated that the K298E mutation affects both protein function and alternative mRNA splicing. Fibroblasts from a skin biopsy of the proband taken at post-mortem were directly induced into neurons (iNs) and expressed both 3-repeat and 4-repeat tau isoforms. As well as contributing new knowledge on MAPT mutations in FTDP-17T, this is the first example of the successful generation of iNs from skin cells retrieved post-mortem

Mutations in valosin-containing protein (VCP) decrease ADP/ATP translocation across the mitochondrial membrane and impair energy metabolism in human neurons

Mutations in the gene encoding valosin-containing protein (VCP) lead to multisystem proteinopathies including frontotemporal dementia. We have previously shown that patient-derived VCP mutant fibroblasts exhibit lower mitochondrial membrane potential, uncoupled respiration, and reduced ATP levels. This study addresses the underlying basis for mitochondrial uncoupling using VCP knockdown neuroblastoma cell lines, induced pluripotent stem cells (iPSCs), and iPSC-derived cortical neurons from patients with pathogenic mutations in VCP. Using fluorescent live cell imaging and respiration analysis we demonstrate a VCP mutation/knockdown-induced dysregulation in the adenine nucleotide translocase, which results in a slower rate of ADP or ATP translocation across the mitochondrial membranes. This deregulation can explain the mitochondrial uncoupling and lower ATP levels in VCP mutation-bearing neurons via reduced ADP availability for ATP synthesis. This study provides evidence for a role of adenine nucleotide translocase in the mechanism underlying altered mitochondrial function in VCP-related degeneration, and this new insight may inform efforts to better understand and manage neurodegenerative disease and other proteinopathies

Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies?

Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Fetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on-going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (i) they often lack synucleinopathy, and (ii) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post-mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α-synuclein mechanisms. Furthermore, these patients are usually younger, slow-progressing, and typically do not suffer from complex non-nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild-type PARKIN expression to re-innervate the striatum. The focal nature of PARKIN-mediated neurodegeneration and lack of active synucleinopathy in most young-onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α-synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy. This article is protected by copyright. All rights reserved.</p

TAGMEMICS (An Introduction to Tagmemics Concepts)

The tagmemics is a unit comprising a function and a class of items fulfilling that function. It is most suitable in describing languages and applied to the description of a very large number of hitherto unrecorded languages. Tagmemics differs from alternative systems of grammatical analysis in that it defines the basic units of language (tagmemes) as composite elements, one part being the “slot,” or “function,” and the other the “filler,” or “class.” One such tagmeme, at the syntactic level of analysis, might be the noun-as-subject (in which the noun is a class that “fills” the subject “slot” in a construction). This article also introduce how tagmemics show for a syntactical counterpart to the phonological and morphological terms, phoneme and morpheme--something at the sentence level which could function as a key identifying unit in the same way that these well- established terms functione

The review of the socio-political fiction novels under binary opposition and logocentrism (case study of novel entitled "Orang-Orang Proyek" by Ahmad Tohari)

The socio-political fiction novel is real and presents an implicit portray of the community's social life of a dwell. This sort of literature is less prevalent because every reader might have their perception while the authors favor particular value according to their social and mental experiences. An Indonesian novel entitled "Orang-Orang Proyek" by Ahmad Tohari, which represents the real condition of the Indonesian community under their political and social situations, is a perfect portray to describe the relation between binary opposition and logocentrism. Both theories will affect the author how they describe each character, even decide how the story ends. This paper tries to break down that literary work using the deconstructive-reading method to read a text with multi-interpretation where the version contains many probabilities of meaning. This study will provide insight into the correct reading method according to the purpose and type of literacy used in literary works