Kesantunan Berbahasa Dalam Bertanya Dan Menjawab Pertanyaan Dalam Webinar

This study aims to explain language politeness in asking and answering questions on webinars. This qualitative research has various research data analyzed by transcribing, inventorying, identifying, classifying, formulating and explaining, as well as concluding and verifying data. Research findings: (1) speech acts of asking and answering questions in the Webinar; (2) the methods used by speakers in the Webinar to form polite speech acts of asking and answering questions. There are two types of speech acts of asking and answering questions, total and partial speech acts. Language politeness strategies focused on asking and answering questions in the Webinar are determined by analyzing speech based on maxims. By complying with the 6 politeness maxims accompanied or not accompanied by prioritizing maxims, the speech act of asking and answering questions is classified as polite

Nrf2/Keap1 Pathway and Expression of Oxidative Stress Lesions 8-hydroxy-2 '-deoxyguanosine and Nitrotyrosine in Melanoma

Background/Aim: Increased expression and prognostic significance of major redox regulator nuclear factor erythroid-2-related factor (Nrf2) is recognized in many cancers. Our aim was to investigate the role of oxidative stress markers in melanoma. Materials and Methods: We characterized the immunohistochemical expression of Nrf2, kelch-like ECH-associated protein 1 (Keap1), BRAF(V600E), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine in 36 nevi, 14 lentigo maligna and 71 malignant melanomas. We measured Nrf2 expression in melanoma cell lines and conducted cytotoxicity assays combining BRAF/NRAS ablation and H2O2 treatment. Results: Nuclear Nrf2 expression in melanoma correlated with deeper Breslow (pPeer reviewe

Novel insights on functions of myotilin/palladin family members

Poikkijuovaisen luuranko- ja sydänlihaksen supistumisyksikkö, sarkomeeri, koostuu tarkoin järjestyneistä aktiini- ja myosiinisäikeistä. Rakenne eroaa muista solutyypeistä, joissa aktiinisäikeistö muovautuu jatkuvasti ja sen järjestyminen säätelee solun muotoa, solujakautumista, soluliikettä ja solunsisäisten organellien kuljetusta. Myotilin, palladin ja myopalladin kuuluvat proteiiniperheeseen, jonka yhteispiirteenä ovat immunoglobuliinin kaltaiset (Igl) domeenit. Proteiinit liittyvät aktiinitukirankaan ja niiden arvellaan toimivan solutukirangan rakenne-elementteinä ja säätelijöinä. Myotilinia ja myopalladinia ilmennetään poikkijuovaisessa lihaksessa. Sen sijaan palladinin eri silmukointimuotoja tavataan monissa kudostyypeissä kuten hermostossa, ja eri muodoilla saattaa olla solutyypistä riippuvia tehtäviä. Poikkijuovaisessa lihaksessa kaikki perheen jäsenet sijaitsevat aktiinisäikeitä yhdistävässä Z-levyssä ja ne sitovat Z-levyn rakenneproteiinia, -aktiniinia. Myotilingeenin pistemutaatiot johtavat periytyviin lihastauteihin, kun taas palladinin mutaatioiden on kuvattu liittyvän periytyvään haimasyöpään ja lisääntyneeseen sydäninfarktin riskiin. Tässä tutkimuksessa selvitettin myotilinin ja pallainin toimintaa. Kokeissa löydettiin uusia palladinin 90-92kDa alatyyppiin sitoutuvia proteiineja. Yksi niistä on aktiinidynamiikkaa säätelevä profilin. Profilinilla on kahdenlaisia tehtäviä; se edesauttaa aktiinisäikeiden muodostumista, mutta se voi myös eristää yksittäisiä aktiinimolekyylejä ja edistää säikeiden hajoamista. Solutasolla palladinin ja profilinin sijainti on yhtenevä runsaasti aktiinia sisältävillä solujen reuna-alueilla. Palladinin ja profilinin sidos on heikko ja hyvin dynaaminen, joka sopii palladinin tehtävään aktiinisäideiden muodostumisen koordinoijana. Toinen palladinin sitoutumiskumppani on aktiinisäikeitä yhteensitova -aktiniini. -Aktiniini liittää solutukirangan solukalvon proteiineihin ja ankkuroi solunsisäisiä viestintämolekyylejä. Sitoutumista välittävä alue on hyvin samankaltainen palladinissa ja myotilinissa. Luurankolihaksen liiallinen toistuva venytys muuttaa Z-levyjen rakennetta ja muotoa. Prosessin aikana syntyy uusia aktiinifilamenttejä sisältäviä tiivistymiä ja lopulta uusia sarkomeereja. Löydöstemme perusteella myotilinin uudelleenjärjestyminen noudattaa aktiinin muutoksia. Tämä viittaa siihen, että myotilin liittää yhteen uudismuodostuvia aktiinisäikeitä ja vakauttaa niitä. Myotilin saattaa myös ankkuroida viesti- tai rakennemolekyylejä, joiden tehtävänä on edesauttaa Z-levyjen uudismuodostusta. Tulostemme perusteella arvelemme, että myotilin toimii Z-levyjen rakenteen vakaajana ja aktiinisäikeiden säätelijänä. Palladinin puute johtaa sikiöaikaiseen kuolemaan hiirillä, mutta myotilinin puutoksella ei ole samanlaisia vaikutuksia. Tuotettujen myotilin poistogeenisten hiirten todetiin syntyvän ja kehittyvän normaalisti eikä niillä esiintynyt rakenteellisia tai toiminnallisia häiriöitä. Toisaalta aiemmissa kokeissa, joissa hiirille on siirretty ihmisen lihastautia aikaansaava myotilingeeni, nähdään samankaltaisia kuin sairailla ihmisillä. Näin ollen muuntunut myotilin näyttä olevan lihaksen toiminnalle haitallisempi kuin myotilinin puute. Myotilinin ja palladinin yhteisvaikutusta selvittääksemme risteytimme myotilin poistegeenisen hiiren ja hiirilinjan, joka ilmentää puutteellisesti palladinin 200 kDa muotoa. Puutteellisesti 200 kDa palladinia ilmentävien hiirten sydänlihaksessa todettiin vähäisiä hienorakenteen muutoksia, mutta risteytetyillä hiirillä tavattiin rakenteellisia ja toiminnallisia muutoksia myös luurankolihaksessa. Tulosten perusteella voidaan todeta, että palladinin 200 kDa muoto säätelee sydänlihassolujen rakennetta. Luurankolihaksessa sen sijaan myotilinilla ja palladinilla näyttäisi olevan päällekkäisiä tehtäviä.In skeletal and cardiac muscle cells, the contractile unit sarcomere consists of actin filaments that have constant length, a strict spatial distribution and are aligned with myosin filaments. Actin filaments from adjacent sarcomeres are cross-linked by actin-associated proteins which form the Z-disk. Sarcomeres provide the muscle cell its shape and they are the structural and functional basis of the muscle contraction. In response to intra- and extracellular stimuli, the actin cytoskeleton is continuously reorganizing in non-muscle or smooth muscle cells in order to determine the cell morphology, the cytokinesis, coordinated cell movements and the intracellular transport of organelles. Myotilin, palladin and myopalladin form a small family of proteins containing immunoglobulin-like (Igl) domains. They are associated with the actin cytoskeleton, and all members of the family are suggested to have roles as a scaffold and as regulators of actin organization. Myotilin and myopalladin are expressed as a single isoform only in the striated muscle. Myotilin expression level is higher in the skeletal muscle than in the heart, while myopalladin expression in higher in the heart than in the skeletal muscle. Their expression levels might be directly correlated with their function. On the contrary, the palladin gene gives rise to several palladin isoforms expressed as a result of alternative splicing events. Palladin is expressed not only in the striated muscle but also in other tissue types, such as the nervous tissue, and different isoforms apparently play cell-specific roles. The three members of the family are localized at the Z-disk in the striated muscle and here they have a common binding partner, the bona-fide Z-disk protein, alpha-actinin. Point mutations in myotilin gene causes muscle disorders of variable phenotype: limb-girdle muscular dystrophy A (LGMD1A), myofibrillar myopathy (MFM) and spheroid body myopathy (SBM). On the other hand, palladin gene mutation has been reported to be associated with familial pancreatic cancer and increased risk for myocardial infarction. In this study we found that, as shown for other poly-L-proline-containing proteins, palladin directly binds a key molecule involved in actin dynamics, profilin. Profilin has a dual function: it is a promoter of actin assembly and it can also act as an actin-sequestring protein resulting in actin depolymerisation. Palladin was shown to interact with profilin via its second polyproline region and, further more, we demonstrated that the interaction is highly dynamic and of low affinity. In cells, palladin colocalized with profilin in actin-rich bundles near cell edges. These results indicate that 90-92 kDa palladin associates with profilin in regions in which novel actin filaments form and that palladin may be involved in the coordination of actin filament formation. Alpha-actinin, an important actin cross-linking molecule, connects the cytoskeleton to transmembrane proteins and serves as a scaffold for signalling molecules. We found that palladin binds to and colocalize with alpha-actinin. The interaction is mediated via a highly conserved region in both myotilin and palladin which is considered as a new binding domain for alpha-actinin. Pain, stiffness and tenderness in the muscle, or delayed onset muscle soreness (DOMS) appears in untrained persons who perform eccentric exercise. All aspects of DOMS are not yet fully understood, however it is considered that new sarcomeres are formed. This process includes modifications in the Z-disk architecture and composition, such as temporary loss of -actinin, titin and nebulin and polymerization of G-actin to form foci of increased F-actin labelling in skeletal muscle fibers after the exercise to finally result in supranumerary sarcomeres. Our studies showed that myotilin follows the widened distribution patterns observed for F-actin, suggesting that myotilin acts as a cross-linker and an F-actin stabilizer. In these structures, myotilin is probably replacing alpha-actinin and, similarly with alpha-actinin, might be an anchoring site for signalling or scaffolding molecules that are recruited to drive the formation of the new sarcomeres. We propose myotilin as a guardian of the Z-disk as apparently myotilin contributes to actin organization in both mature and forming Z-disks. To further study the functions of myotilin we generated knockout mice. While loss of all palladin isoforms leads to embryonical lethality in mice, we showed that myotilin knockout mouse survives and has no obvious morphological or functional alteration in striated muscle or other organs. Myotilin absence is apparently compensated by other proteins, possibly by members of myotilin/palladin/myopalladin subfamily. This finding is in concordance with the finding that the transgenic expression of a mutant myotilin leads to morphological alterations observed in myotilinopathies, i.e. mutated myotilin appears to have a toxic effect on the structure of the skeletal muscle, whereas myopathy due to myotilin deficiency has not been reported. Further, we have generated and investigated a mouse that lacks myotilin and expresses low levels of the 200 kDa palladin. While the 200 kDa palladin hypomorph mice shows ultrastructural modifications of the heart architecture, we showed that combined absence of myotilin and low levels of 200 kDa palladin led to morphological and functional alterations in skeletal muscle. This work showed that 200 kDa palladin has an important role in the maintenance of normal architecture of the cardiomyocytes and that myotilin deficiency apparently exacerbated the cardiomyocyte defects. This indicates that in skeletal muscle myotilin and 200 kDa palladin may have a similar function, while in the heart their functions might be different

Targeted Deletion of the Muscular Dystrophy Gene myotilin Does Not Perturb Muscle Structure or Function in Mice

Myotilin, palladin, and myopalladin form a novel small subfamily of cytoskeletal proteins that contain immunoglobulin-like domains. Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells. The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere. Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myofibrillar myopathy. Here we describe the generation and analysis of mice that lack myotilin, myo(−/−) mice. Surprisingly, myo(−/−) mice maintain normal muscle sarcomeric and sarcolemmal integrity. Also, loss of myotilin does not cause alterations in the heart or other organs of newborn or adult myo(−/−) mice. The mice develop normally and have a normal life span, and their muscle capacity does not significantly differ from wild-type mice even after prolonged physical stress. The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent

Schistosomiasis in a Low Prevalence Area: Incomplete Urbanization Increasing Risk of Infection in Paracambi, RJ, Brazil

The risk of schistosomiasis infection and heavy infection in the locality of Sabugo was evaluated in relation to housing in areas with different urbanization development and to residential supply with snail-infested water. Critical sanitary conditions were found in areas of incomplete urbanization, where healthy water supply sources were scarce, and draining of sewage, without previous treatment, was made directly to the water-bodies used for domestic and leisure activities, despite being Biomphalaria tenagophila snail breeding-places. Stool examinations (Kato-Katz and Lutz methods) showed prevalence of 2.9%, mean intensity of 79 eggs per gram of stool and 47% of positive cases presenting intense infection. The use of snail-contaminated water for domestic purposes was considered a risk factor for infection. It is concluded that incomplete urbanization would facilitate transmission, probably enhancing the intensity of infection and that a low prevalence could hide a highly focal transmission. The relevance of these facts upon the efficiency of epidemiologic study methods and disease control planning are then discussed. Key words