Memet Fuat, Piraye ve Nazım

Taha Toros Arşivi, Dosya Adı: Nazım Hikmetİstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033

看護師の類似薬剤名に対する識別の正確性 : 薬剤名への指差呼称の影響

首都大学東京, 2018-03-25, 博士（学術）, 甲第823号首都大学東

Roles and Cellular Localization of GBP2 and NAB2 During the Blood Stage of Malaria Parasites

The quality control and export of mRNA by RNA-binding proteins are necessary for the survival of malaria parasites, which have complex life cycles. Nuclear poly(A) binding protein 2 (NAB2), THO complex subunit 4 (THO4), nucleolar protein 3 (NPL3), G-strand binding protein 2 (GBP2) and serine/arginine-rich splicing factor 1 (SR1) are involved in nuclear mRNA export in malaria parasites. However, their roles in asexual and sexual development, and in cellular localization, are not fully understood. In this study using the rodent malaria parasite, Plasmodium berghei, we found that NAB2 and SR1, but not THO4, NPL3 or GBP2, played essential roles in the asexual development of malaria parasites. By contrast, GBP2 but not NPL3 was involved in male and female gametocyte production. THO4 was involved in female gametocyte production, but had a lower impact than GBP2. In this study, we focused on GBP2 and NAB2, which play important roles in the sexual and asexual development of malaria parasites, respectively, and examined their cellular localization. GBP2 localized to both the nucleus and cytoplasm of malaria parasites. Using immunoprecipitation coupled to mass spectrometry (IP-MS), GBP2 interacted with the proteins ALBA4, DOZI, and CITH, which play roles in translational repression. IP-MS also revealed that phosphorylated adapter RNA export protein (PHAX) domain-containing protein, an adaptor protein for exportin-1, also interacted with GBP2, implying that mRNA export occurs via the PHAX domain-containing protein pathway in malaria parasites. Live-cell fluorescence imaging revealed that NAB2 localized at the nuclear periphery. Moreover, IP-MS indicated that NAB2 interacted with transportin. RNA immunoprecipitation coupled to RNA sequencing revealed that NAB2 bound directly to 143 mRNAs, including those encoding 40S and 60S ribosomal proteins. Our findings imply that malaria parasites use an evolutionarily ancient mechanism conserved throughout eukaryotic evolution.journal articl

Involvement of RNA-binding protein Hfq in the osmotic-response regulation of invE gene expression in Shigella sonnei

<p>Abstract</p> <p>Background</p> <p>The expression of Type III secretion system (TTSS) in <it>Shigella </it>is regulated in response to changes in environmental osmolarity and temperature. Temperature-dependent regulation of <it>virF</it>, the master regulator of TTSS synthesis, is believed to occur at the transcriptional level. We recently demonstrated, however, that TTSS synthesis also involves post-transcriptional regulation of the synthesis of InvE, a target of <it>virF </it>and key regulator of TTSS synthesis. The mRNA levels of <it>invE </it>(<it>virB</it>) are stable at 37°C, but mRNA stability markedly decreases at low temperatures where the TTSS synthesis is tightly repressed. Deletion of <it>hfq</it>, which encodes an RNA chaperone in Gram-negative bacteria, results in the restoration of expression of <it>invE </it>and other TTSS genes at low temperature due to an increase in the stability of <it>invE </it>mRNA. To date, the molecular details of the regulation of TTSS expression in response to osmotic pressure are not known. In the current study, we investigated the mechanism of regulation of TTSS by osmotic pressure.</p> <p>Results</p> <p>Transcription of <it>virF</it>, which encodes the master regulator of TTSS expression, was partially repressed under low osmotic conditions. Several lines of evidence indicated that osmolarity-dependent changes in TTSS synthesis are controlled at the post-transcriptional level, through the regulation of InvE synthesis. First, the expression InvE protein was tightly repressed under low osmotic growth conditions, even though <it>invE </it>mRNA transcripts were readily detectable. Second, under low osmotic conditions, <it>invE </it>mRNA was rapidly degraded, whereas deletion of <it>hfq</it>, which encodes an RNA chaperone, resulted in increased <it>invE </it>mRNA stability and the production of InvE protein. Third, the binding of purified Hfq <it>in vitro </it>to <it>invE </it>RNA was stronger in low-salt buffer, as assessed by gel-shift analysis and surface plasmon resonance (Biacore analysis).</p> <p>Conclusion</p> <p>Osmolarity-dependent changes in TTSS synthesis in <it>Shigella </it>involve the post-transcriptional regulation of InvE expression, in addition to partial transcriptional activation by <it>virF</it>. The stability of <it>invE </it>mRNA is reduced under low osmotic conditions, similar to the effect of temperature. Deletion of an RNA chaperone gene (<it>hfq</it>) abolished the repression of TTSS synthesis at low osmolarity through a mechanism that involved increased stability of <it>invE </it>mRNA. We propose that the expression of <it>Shigella </it>virulence genes in response to both osmolarity and temperature involves the post-transcriptional regulation of expression of InvE, a critical regulator of TTSS synthesis.</p

Neurophysiological modeling of bladder afferent activity in the rat overactive bladder model

The overactive bladder (OAB) is a syndrome-based urinary dysfunction characterized by “urgency, with or without urge incontinence, usually with frequency and nocturia”. Earlier we developed a mathematical model of bladder nerve activity during voiding in anesthetized rats and found that the nerve activity in the relaxation phase of voiding contractions was all afferent. In the present study, we applied this mathematical model to an acetic acid (AA) rat model of bladder overactivity to study the sensitivity of afferent fibers in intact nerves to bladder pressure and volume changes. The afferent activity in the filling phase and the slope, i.e., the sensitivity of the afferent fibers to pressure changes in the post-void relaxation phase, were found to be significantly higher in AA than in saline measurements, while the offset (nerve activity at pressure ~0) and maximum pressure were comparable. We have thus shown, for the first time, that the sensitivity of afferent fibers in the OAB can be studied without cutting nerves or preparation of single fibers. We conclude that bladder overactivity induced by AA in rats is neurogenic in origin and is caused by increased sensitivity of afferent sensors in the bladder wall

Malaria in the postpartum period causes damage to the mammary gland

Mastitis is an inflammation of the mammary gland in the breast and is typically due to bacterial infection. In malaria-endemic areas, mastitis with accompanying fever can be challenging to differentiate from malaria. At the same time, it is unclear whether malaria infection is directly involved in the development of mastitis. In the present study, whether mastitis develops during infection with malaria parasites was investigated using a rodent malaria model with Plasmodium berghei (P. berghei; Pb) ANKA. The course of parasitemia in postpartum mice infected with Pb ANKA was similar to the course in infected virgin mice. However, infected postpartum mice died earlier than did infected virgin mice. In addition, the weight of pups from mice infected with Pb ANKA was significantly reduced compared with pups from uninfected mice. The macroscopic and histological analyses showed apparent changes, such as destruction of the alveolus wall and extensive presence of leukocytes, in mammary gland tissue in mice infected during the postpartum period. The findings suggest that women during the postpartum period are more vulnerable to complications when infected with malaria parasites, particularly women who do not acquire protective immunity against malaria parasites. Based on the proteomic analysis, IFN-γ signaling pathway-related proteins in mammary gland tissue of the infected postpartum mice were increased. Our results indicate that inflammation induced by IFN-γ, a proinflammatory cytokine, may contribute to negative histological changes in mammary gland tissue of postpartum mice infected with Pb ANKA. In IFN-γ receptor 1-deficient (IFNGR1-KO) mice, the histological changes in mammary gland tissue of the infected postpartum wild-type mice were improved to almost normal mammary gland structure. Furthermore, weight loss in pups delivered by infected IFNGR1-KO postpartum mice was not observed. Taken together, these findings indicate that inflammation induced by IFN-γ is associated with development of mastitis in postpartum mice infected with Pb ANKA. The present study results may increase our understanding of how disease aggravation occurs during postpartum malaria.journal articl

Professional and novice audio describers: quality assessments and audio interactions

Empowering novice describers can reduce costs and expand access to high-quality audio descriptions (ADs). This study explored differences between novice and professional practices by analysing their ADs for a 3:42-minute scene from a Japanese fictional film. A film producer rated both the overall quality and volume quality of ADs. The perceived AD volume quality reflects the comprehensive volume experience within ADs beyond loudness. The assessment revealed that ADs created by ten novices using speech synthesis reached approximately 60% of both the overall quality and volume quality of published ADs with human voice. Kernel density estimation showed significantly lower mean loudness in published ADs than in novice ADs. Additionally, a significant negative correlation existed between perceived AD volume quality and mean film loudness during AD presentation across all AD sets. However, published ADs had longer durations compared to novice ADs. Contrasting cueing strategies were observed. Published ADs relied on film sounds, whereas novice ADs leaned on visual cues. Consequently, we developed a professional technique: carefully curating the film information to be heard and balancing AD placement to ensure the audio experience of both ADs and film sound without abrupt AD loudness increases. This sonic approach empowers novices to craft impactful ADs

Characterization of a nuclear transport factor 2-like domain-containing protein in Plasmodium berghei

Background Plasmodium lacks an mRNA export receptor ortholog, such as yeast Mex67. Yeast Mex67 contains a nuclear transport factor 2 (NTF2)-like domain, suggesting that NTF2-like domain-containing proteins might be associated with mRNA export in Plasmodium. In this study, the relationship between mRNA export and an NTF2-like domain-containing protein, PBANKA_1019700, was investigated using the ANKA strain of rodent malaria parasite Plasmodium berghei. Methods The deletion mutant Δ1019700 was generated by introducing gene-targeting vectors into the P. berghei ANKA genome, and parasite growth and virulence were examined. To investigate whether PBANKA_1019700 is involved in mRNA export, live-cell fluorescence imaging and immunoprecipitation coupled to mass spectrometry (IP-MS) were performed using transgenic parasites expressing fusion proteins (1019700::mCherry). Results Deletion of PBANKA_1019700 affected the sexual phase but not the asexual phase of malaria parasites. Live-cell fluorescence imaging showed that PBANKA_1019700 localizes to the cytoplasm. Moreover, IP-MS analysis of 1019700::mCherry indicated that PBANKA_1019700 interacts with ubiquitin-related proteins but not nuclear proteins. Conclusions PBANKA_1019700 is a noncanonical NTF2-like superfamily protein.journal articl

Impact of the 2011 tsunami on the littoral system around offshore breakwaters on Sendai Coast

After the 2011 Great East Japan Earthquake Tsunami, littoral system on Sendai Coast have been changing due to tsunami-induced highly non-equilibrium condition along the coast. In order to clarify the modification of littoral environment and its subsequent recovery on Sendai Coast, analysis of shoreline change has been carried out. In this study, the shoreline was extracted from frequently captured aerial photographs from 2009 until now, and analysis using an empirical orthogonal function (EOF) method was conducted. It is seen that the shoreline retreated greatly due to tsunami event. In particular, tombolo which existed behind the offshore breakwater completely disappeared due to the tsunami. Total of contribution of the 1st and 2nd EOF components is more than 70%. It is concluded that the 1st component originated from cross-shore sediment movement, while the 2nd component represents longshore sediment transport. Although the 1st component shows only slight modification after the tsunami, the 2nd component resulting from a longshore sediment transport shows distinct change after the tsunami around the offshore breakwaters