Pelanggaran Prinsip Kerjasama pada Implikatur Percakapan dalam Drama “Seigi No Mikata” Episode 1

Kata Kunci : pragmatik, pelanggaran prinsip kerjasama, implikatur, implikatur percakapan,. Manusia tidak bisa lepas dari bahasa dan komunikasi. Hubungan bahasa dan komunikasi termasuk dalam wilayah pragmatik. Terdapat dua prinsip dalam kajian pragmatik, yaitu prinsip kerjasama dan prinsip kesantunan. Pelanggaran terhadap prinsip tersebut disebut juga implikatur. Implikatur yang paling banyak ditemukan dalam komunikasi adalah implikatur percakapan. Oleh karena itu penelitian mengenai “ Pelanggaran Prinsip Kerjasama pada Implikatur Percakapan dalam Drama Seigi no Mikata Episode 1” ini dilakukan. Untuk menjawab rumusan masalah (1) Bagaimana pelanggaran prinsip kerjasama yang terdapat dalam implikatur percakapan dalam drama “Seigi no Mikata” dan (2) Apa saja fungsi pragmatik dalam implikatur percakapan dalam drama “Seigi no Mikata”. Penelitian ini merupakan jenis penelitian deskriptif kualitatif. Yang bertujuan menganalisis pelanggaran prinsip kerjasama yang terdapat dalam implikatur percakapan. Hasil penelitian menunjukkan terdapat 20 implikatur percakapan. Masing-masing melanggar prinsip kerjasama Grice dengan rincian, 5 pelanggaran maksim kuantitas, 6 maksim kualitas, 4 maksim relevansi dan 5 maksim pelaksanaan. Fungsi pragmatik dalam implikatur percakapan tersebut adalah asertif, direktif, komisif dan ekspresif, tidak ditemukan fungsi deklaratif. Dalam penelitian berikutnya diharapkan ada penelitian mengenai pelanggaran prinsip kesantunan. Objek kajian selain drama juga bisa dilakukan

Assessment of Nutritional Status and Anemia in Children with Congenital Heart Disease

INTRODUCTION: Congenital heart defect (CHD) is the most common defect among all birth defects representing a major global health problem. Twenty-eight percent of all major congenital anomalies comprise of heart defects. Congenital heart disease (Cyanotic and Acyanotic) occurs in approximately 0.8% of live births.In India, the prevalence of CHD is not uniform across the country and varies from 0.8 to 5.2/1000 patients in community-based studies while the prevalence ranges between 3.9 and 26.4/1000 live births in hospital-based studies in India, which is not uniform across the country. The burden of CHD is high in developing countries like India, due to the high birth rate and critical nature of CHD requiring expensive surgical and non-surgical interventions. CHD is considered a real challenge because of the complex interplay between medical, surgical, dietetic and socio-economic factors. AIMS AND OBJECTIVES: 1. To find out the Nutritional Status in children (1-12years) with congenital heart disease by using anthropometric measurements, clinical assessment and dietary evaluation. 2. To assess degree and type of Anemia in children with congenital heart disease using assessment of hemoglobin, red cell indices, red cell distribution width and peripheral smear. METHODS: We conducted an cross sectional study of 80 children aged 1-12 years of age with congenital heart disease chosen by purposive sampling technique,attending as Outpatient and Inpatient in the Department of Peadiatrics, Sree Mookambika Institute of Medical Sciences, Kulasekharam. over a period of 18 months. RESULTS: In this study on 80 children, 63.8 % were in the age group 1-12 years whereas 36.2% belonged to age group 12mon-59mon.The male to female ratio was 1:1. 81.3% had ACHD; out of which VSD was the most common (35%).18.7% had CCHD, out of which TOF was the most common (13.7%).69.2% of ACHD were underweight in comparison to 35.7% in CCHD.with significant p value 0.025,42.9% of ACHD were stunted in comparison to 57.1% in CCHD with significant p value of 0.004, 80% of ACHD were wasted in comparion to 20% wasted in CCHD. 21.3% of ACHD had anemia 17.5% of CCHD had polycythemia. 21.2% had decreased red cell indices indicating microcytic hypochromic and 36.2% had increased RDW with p value 0.000 indicating nutritional anemia. According to Peripheral smear, 16.2% had microcytic hypochromic anemia. CONCLUSION: Congenital heart defect (CHD) is the most common congenital malformation among all birth defects leading to morbidity and mortality among children. The burden of CHD is high in developing countries like India, due to the high birth rate and critical nature of CHD requiring expensive surgical and non-surgical interventions. Malnutrition and anemia is rampant among children with CHD with a significant impact on the intervention and the outcome of intervention. The high proportion of malnutrition and anemia among children with CHD warrants proper evaluation and early intervention. This is of utmost importance as majority of CHD are likely to get surgical and non surgical intervention under the RBSK scheme. The RBSK scheme also focuses on malnutrition and deficiency disorder. Accreditation of private institution under the RBSK scheme for intervention of CHD is a big boon to the community

Infergen stimulated macrophages restrict Mycobacterium tuberculosis growth by autophagy and release of nitric oxide

IFN alfacon-1 (Infergen) is a synthetic form of Interferon (IFN)-α2b. Infergen has immunomodulatory activity and is effective against hepatitis C virus. However, the effect of Infergen (IFG) on Mycobacterium tuberculosis (Mtb) has not yet been reported. Therefore, for the first time, we have studied the influence of IFG in constraining the survival of Mtb in human macrophages. We observed that IFG significantly enhanced the maturation and activation of macrophages. Further, it substantially augmented the secretion of IL-6, Nitric Oxide (NO) and antigen uptake. Moreover, macrophages exhibited remarkably higher bactericidal activity, as evidenced by reduction in the Mtb growth. Infergen-mediated mechanism was different from the type-1 interferons; since it worked through the activation of NF-κB, phosphorylation of STAT-3 and Akt-PI3K that improved the bactericidal activity through autophagy and NO release. In future, IFG immunotherapy can be a novel strategy for treating patients and controlling TB

Curdlan Limits Mycobacterium tuberculosis Survival Through STAT-1 Regulated Nitric Oxide Production

Host-directed therapies have emerged as an innovative and promising approach in tuberculosis (TB) treatment due to the observed limitations of current TB regimen such as lengthy duration and emergence of drug resistance. Thus, we explored the role of curdlan (beta glucan polysaccharide) as a novel strategy to activate macrophages against Mycobacterium tuberculosis (Mtb). The aim of the study was to investigate the role of curdlan in restricting the Mtb growth both in vitro and in vivo. Further, the immunomodulatory potential of curdlan against Mtb and the underlying mechanism is largely unknown. We found that curdlan treatment enhanced the antigen presentation, pro-inflammatory cytokines, Mtb uptake and killing activity of macrophages. In vivo studies showed that curdlan therapy significantly reduced the Mtb burden in lung and spleen of mice. Administration of curdlan triggered the protective Th1 and Th17 immunity while boosting the central and effector memory response in Mtb infected mice. Curdlan mediated anti-Mtb activity is through signal transducer and activator of transcription-1 (STAT-1), which regulates nitric oxide (NO) production through inducible NO synthase (iNOS) induction; along with this activation of nuclear factor kappa B (NF-κB) was also evident in Mtb infected macrophages. Thus, we demonstrate that curdlan exerts effective anti-tuberculous activity anti-tuberculous activity. It can be used as a potential host-directed therapy against Mtb

Triggering through NOD-2 differentiates bone marrow precursors to dendritic cells with potent bactericidal activity

Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naïve T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-αβ signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens

Signaling through NOD-2 and TLR-4 bolsters the T cell priming capability of dendritic cells by inducing autophagy

T cells play a cardinal role in mediating protection against intracellular pathogens like Mycobacterium tuberculosis (Mtb). It is important to understand the factors that govern the T cell response; thereby can modulate its activity. Dendritic cells (DCs) are the major player in initiation and augmentation of T cell response. Targeting DCs to induce their optimum maturation and activation can lead to a better T cell response. Interestingly, we observed that combinatorial signaling of DCs through NOD-2 and TLR-4 fortified better yield of IL-12p40/70, IL-6 and IFN-γ and upregulated the expression of CD40, CD80 and CD86 costimulatory molecules. Further, we noticed improved phagocytic capabilities of DCs. Furthermore, NOD-2 and TLR-4 induced autophagy in DCs, which enhanced the activation of T cells. This study signifies that NOD-2 and TLR-4 exhibit synergism in invigorating the activity of DCs. Consequently, this strategy may have significant immunotherapeutic potential in bolstering the function of DCs and thus improving the immunity against pathogens

MicroRNA-222 reprogrammed cancer-associated fibroblasts enhance growth and metastasis of breast cancer

BACKGROUND: Cancer-associated fibroblasts (CAFs) are known to impact on tumour behaviour, but the mechanisms controlling this are poorly understood. METHODS: Breast normal fibroblasts (NFs) or CAFs were isolated from cancers by laser microdissection or were cultured. Fibroblasts were transfected to manipulate miR-222 or Lamin B receptor (LBR). The fibroblast-conditioned medium was collected and used to treat epithelial BC lines MDA-MB-231 and MDA-MB-157. Migration, invasion, proliferation or senescence was assessed using transwell, MTT or X-gal assays, respectively. RESULTS: MiR-222 was upregulated in CAFs as compared with NFs. Ectopic miR-222 expression in NFs induced CAF-like expression profiles, while miR-222 knockdown in CAFs inhibited CAF phenotypes. LBR was identified as a direct miR-222 target, and was functionally relevant since LBR knockdown phenocopied miR-222 overexpression and LBR overexpression phenocopied miR-222 knockdown. MiR-222 overexpression, or LBR knockdown, was sufficient to induce NFs to show the CAF characteristics of enhanced migration, invasion and senescence, and furthermore, the conditioned medium from these fibroblasts induced increased BC cell migration and invasion. The reverse manipulations in CAFs inhibited these behaviours in fibroblasts, and inhibited paracrine influences on BC cells. CONCLUSION: MiR-222/LBR have key roles in controlling pro-progression influences of CAFs in BC. This pathway may present therapeutic opportunities to inhibit CAF-induced cancer progression

JNK1 Phosphorylates SIRT1 and Promotes Its Enzymatic Activity

SIRT1 is a NAD-dependent deacetylase that regulates a variety of pathways including the stress protection pathway. SIRT1 deacetylates a number of protein substrates, including histones, FOXOs, PGC-1α, and p53, leading to cellular protection. We identified a functional interaction between cJUN N-terminal kinase (JNK1) and SIRT1 by coimmunoprecipitation of endogenous proteins. The interaction between JNK1 and SIRT1 was identified under conditions of oxidative stress and required activation of JNK1 via phosphorylation. Modulation of SIRT1 activity or protein levels using nicotinamide or RNAi did not modify JNK1 activity as measured by its ability to phosphorylate cJUN. In contrast, human SIRT1 was phosphorylated by JNK1 on three sites: Ser27, Ser47, and Thr530 and this phosphorylation of SIRT1 increased its nuclear localization and enzymatic activity. Surprisingly, JNK1 phosphorylation of SIRT1 showed substrate specificity resulting in deacetylation of histone H3, but not p53. These findings identify a mechanism for regulation of SIRT1 enzymatic activity in response to oxidative stress and shed new light on its role in the stress protection pathway

Effect of calcium doping on the anodic behavior of E-AlMgSi (Aldrey) conducting aluminum alloy in NaCl electrolyte medium

The design of new materials intended for operation under severe conditions faces the task of rendering the materials corrosion resistant. The practical solution of this task is interrelated with the knowledge of corrosion protection of metals and alloys. The use of conducting aluminum alloys for the manufacture of thin wire may encounter specific problems. This is caused by the insufficient strength of these alloys and a small number of kinks before fracture. Aluminum alloys have been developed in recent years which even in a soft state have strength characteristics that allow them to be used as a conductive material. The E-AlMgSi (Aldrey) aluminum alloy is a well-known conducting alloy. This alloy is a heat-strengthened one, possessing good plasticity and high strength. After appropriate heat treatment this alloy acquires high electrical conductivity. Wires made from this alloy are almost exclusively used for air transmission lines. This work presents data on the corrosion behavior of calcium containing E-AlMgSi (Aldrey) aluminum conducting alloy in 0.03, 0.3 and 3.0% NaCl electrolyte medium. The anodic behavior of the alloy has been studied using a potentiostatic technique with a PI-50-1.1 potentiostat at a 2 mV/s potential sweep rate. Calcium doping of the E-AlMgSi (Aldrey) aluminum alloy increases its corrosion resistance by 15–20%. The corrosion, pitting and repassivation potentials of calcium doped alloys shift toward the positive region. An increase in the sodium chloride electrolyte concentration leads to a decrease in these potentials

A longitudinal study of transitions between smoking and smokeless tobacco use from the ITC Bangladesh Surveys: implications for tobacco control in the Southeast Asia region

Background In Southeast Asia, tobacco use is a major public health threat. Tobacco users in this region may switch between or concurrently use smoked tobacco and smokeless tobacco (SLT), which makes effective tobacco control challenging. This study tracks transitions of use among different product users (cigarettes, bidis, and SLT) in Bangladesh, one of the largest consumers of tobacco in the region, and examines factors related to transitions and cessation. Methods Four waves (2009–2015) of the International Tobacco Control (ITC) Bangladesh Survey with a cohort sample of 3245 tobacco users were analysed. Generalized Estimating Equations (GEE) models were used to explore the socioeconomic correlates of transitions from the exclusive use of cigarettes, bidis, or SLT to the use of other tobacco products or quitting over time. Findings Among exclusive cigarette users, most remained as exclusive cigarette users (68.1%). However, rural smokers were more likely than urban smokers to transition to bidi use (odds ratio [OR] = 3.02, 95% confidence interval [CI] = 1.45–6.29); to SLT use (OR = 2.68, 95% CI = 1.79–4.02) and to quit tobacco (OR = 1.57, 95% CI = 1.06–2.33). Among exclusive bidi users, transitional patterns were more volatile. Fewer than half (43.3%) of the exclusive bidi users maintained their status throughout the waves. Those with higher socio-economic status (SES) were more likely to quit (OR = 4.16, 95% CI = 1.08–13.12) compared to low SES smokers. Exclusive SLT users either continued using SLT or quit with minimal transitions to other products (≤2%). Nevertheless, males were more likely to switch to other tobacco products; younger (OR = 2.94, 95% CI = 1.23–6.90 vs. older), more educated (OR = 1.55, 95% CI = 1.77–3.12 vs. less educated), and urban SLT users (OR = 0.52, 95% CI = 0.30–0.86 for rural vs. urban users) were more likely to quit. Interpretation Complex transitional patterns were found among different types of tobacco product users over time in Bangladesh. These findings can inform more comprehensive and multi-faceted approaches to tackle diversified tobacco use in Bangladesh and neighbouring countries in the Southeast Asia region with similar tobacco user profiles of smoked tobacco and SLT products