220 research outputs found
Systematic minimization of RNA ligase ribozyme through large-scale design-synthesis-sequence cycles
Template-directed RNA ligation catalyzed by an RNA enzyme (ribozyme) is a plausible and important reaction that could have been involved in transferring genetic information during prebiotic evolution. Laboratory evolution experiments have yielded several classes of ligase ribozymes, but their minimal sequence requirements remain largely unexplored. Because selection experiments strongly favor highly active sequences, less active but smaller catalytic motifs may have been overlooked in these experiments. We used large-scale DNA synthesis and high-throughput ribozyme assay enabled by deep sequencing to systematically minimize a previously laboratory-evolved ligase ribozyme. After designing and evaluating >10 000 sequences, we identified catalytic cores as small as 18 contiguous bases that catalyze template-directed regiospecific RNA ligation. The fact that such a short sequence can catalyze this critical reaction suggests that similarly simple or even simpler motifs may populate the RNA sequence space which could have been accessible to the prebiotic ribozymes
Premium Bashōfu and Rough Bashōfu : Producing, wearing, and discussing bashōfu, a traditional banana fiber textile from Okinawa
Session IV : Crafts as Cultural ResourcesBashōfu is woven from threads of fibers extracted from the Itobashō wild banana plant (Musa balbisiana var. liukiuensis). Because clothing made of bashōfu is light and breathable, all classes of people of the Ryukyu Kingdom (1429 - 1879) favored it in the highly humid summer. Bashōfu was roughly classified into two quality levels: premium bashōfu for high-class people’s clothing and for trading, and rough bashōfu for the masses. Nowadays only premium bashōfu is produced as a sophisticated traditional craft in Okinawa, and attracts both academic and public interest. We have, however, proceeded with scientific research into rough bashōfu to investigate the potential of rough bashōfu as a wearable textile. Why has rough bashōfu been overlooked up to now? Some attention was paid to bashōfu by the mingei (folk craft) movement and the Japanese kimono market, but only in general, which led to rough bashōfu for the common people being neglected or forgotten. In 1942, during the Pacific War, the Japanese philosopher and the mingei movement leader Sōetsu Yanagi published The Story of Bashōfu, in which he praised its beauty and authenticity. However, he did not distinguish premium bashōfu from the rough type, and simply stated that the best place for bashōfu production was the former capital, Shuri, because clothing for the royal family had been produced there. After the collapse of bashōfu production following the 1945 Battle of Okinawa and the subsequent US military occupation, Toshiko Taira, who was encouraged by the the mingei movement, succeeded in re-starting bashōfu production in Kijoka, Okinawa around 1950. Thereafter, she and her colleagues met the demand from US soldiers, and in the late 20th century, from the Japanese kimono market. The Japanese government designated Bashōfu in Kijoka as an Important Intangible Cultural Property in 1974, two years after Okinawa’s reversion to Japanese administration from the US military government. In this study, we will examine reasons why rough bashōfu had been neglected in Okinawan and Japanese history and look at its potential as a future textile
Assessing the Impact of Parental Depressive Symptoms on Offspring Temperament and Development in Infancy
The study prospectively followed 135 women during their pregnancy and their offspring till 6 months of age, to examine the roles of maternal and paternal depression during pregnancy on offspring neurobehavioral development as measured by their early temperament. Maternal and paternal depression statuses were ascertained during the third trimester, and infant temperament was evaluated at 6 months, via mothers self-report. Multivariable general linear model was used to assess 1) the main effects of maternal and paternal depression on infant temperament and 2) the interaction effect between maternal and paternal depression on infant temperament. Results show that maternal depression, but not paternal depression, was directly associated with greater neurobehavioral impairment in offspring as evident by more difficult temperament, including lower Smiling and Laughter (p= .006), lower Soothability (p= .02), elevated Sadness (p= .04) and lower Vocal Reactivity (p= .001). Moreover, only in the presence of maternal depression, was paternal depression significantly associated with signs of offspring neurobehavioral impairment, including lower Smiling and Laughter (p= .01) lower High Pleasure Seeking (p= .03), lower Soothability (p= .05), lower Cuddliness (p= .05) and lower Vocal Reactivity (p\u3c .0001). These findings suggest that maternal, but not paternal, depression was directly associated with infant neurobehavioral impairment. Significant interaction effect suggests that in the presence of maternal depression, paternal depression amplifies its negative valence on infant neurobehavioral development. Providing intervention services not only for depressed mothers but also their partners during pregnancy may prove to be an effective prevention strategy for suboptimal neurobehavioral development in offspring
A Case of Acquired Leucoderma, Associated with Hashimoto's Thyroiditis
A 67-year-old female diagnosed as Hashimoto's thyroiditis in company with acquired leucoderma was reported. She first noticed the enlarged thyroid at the age of 36, and thereafter leucoderma made its appearance 30 years later. Though a significant association between these two diseases has been found in the literature thus far and they are considered to be of autoimmune origin, their coexistence is not so common clinically. In spite of PUVA treatment, a benefit effect was not obtained completely
Mitochondrial Gene Expression Profiles Are Associated with Maternal Psychosocial Stress in Pregnancy and Infant Temperament
Background Gene-environment interactions mediate through the placenta and shape the fetal brain development. Between the environmental determinants of the fetal brain, maternal psychosocial stress in pregnancy has been shown to negatively influence the infant temperament development. This in turn may have adverse consequences on the infant neurodevelopment extending throughout the entire life-span. However little is known about the underlying biological mechanisms of the effects of maternal psychosocial stress in pregnancy on infant temperament. Environmental stressors such as maternal psychosocial stress in pregnancy activate the stress response cascade that in turn drives the increase in the cellular energy demand of vital organs with high metabolic rates such as, in pregnancy, the placenta. Key players of the stress response cascade are the mitochondria. Results Here, we tested the expression of all 13 protein-coding genes encoded by the mitochondria in 108 placenta samples from the Stress in Pregnancy birth cohort, a study that aims at determining the influence of in utero exposure to maternal psychosocial stress in pregnancy on infant temperament. We showed that the expression of the protein-coding mitochondrial-encoded gene MT-ND2 was positively associated with indices of maternal psychosocial stress in pregnancy including Prenatal Perceived Stress (β = 0.259; p-regression = 0.004; r2-regression = 0.120), State Anxiety (β = 0.218; p-regression = 0.003; r2-regression = 0.153), Trait Anxiety (β = 0.262; p-regression = 0.003; r2-regression = 0.129) and Pregnancy Anxiety Total (β = 0.208; p-regression = 0.010; r2-regression = 0.103). In the meantime MT-ND2 was negatively associated with the infant temperament indices of Activity Level (β = -0.257; p-regression = 0.008; r2-regression = 0.165) and Smile and Laughter (β = -0.286; p-regression = 0.036; r2-regression = 0.082). Additionally, MT-ND6 was associated with the maternal psychosocial stress in pregnancy index of Prenatal Perceived Stress (β = -0.231; p-regression = 0.004; r2-regression = 0.120), while MT-CO2 was associated with the maternal psychosocial stress in pregnancy indices of State Anxiety (β = 0.206; p-regression = 0.003; r2-regression = 0.153) and Trait Anxiety (β = 0.205; p-regression = 0.003; r2-regression = 0.129). Conclusions Our data support the role of mitochondria in responding to maternal psychosocial stress in pregnancy, as assessed in placenta, while also suggesting an important role for the mitochondria in the infant temperament development
Self-powered RNA nanomachine driven by metastable structure
Many non-coding and regulatory RNA elements have evolved to exploit transient or metastable structures that emerge during transcription to control complex folding pathways or to encode dynamic functions. However, efforts to engineer synthetic RNA devices have mostly focused on the thermodynamically stable structures. Consequently, significant challenges and opportunities exist in engineering functional RNAs that explicitly take advantage of cotranscriptionally generated transient or metastable structures. In this work, we designed a short RNA sequence that adopts a robust metastable structure when transcribed by an RNA polymerase. Although the metastable structure persists for hours at low temperature, it refolds almost completely into the thermodynamically stable structure upon heat denaturation followed by cooling. The synthetic RNA was also equipped with the Broccoli aptamer so that it can bind its ligand and become fluorescent only in the thermodynamically stable structure. We further demonstrated that the relaxation to the thermodynamically stable and fluorescent structure can be catalyzed by a short trigger RNA in a sequence-specific manner. Finally, the RNA architecture was redesigned to sense and respond to microRNA sequences. In summary, we designed RNA nanomachines that can detect an RNA sequence, amplify signal and produce an optical output, all encoded in a single RNA transcript, self-powered by a metastable structure
Direct screening for ribozyme activity in mammalian cells
Engineered ribozymes are powerful tools for manipulating gene expression in living cells. However, identification of active ribozymes in mammalian cells has relied on empirical assays of a limited number of arbitrarily chosen ribozymes. Here, we synthesized 376 natural and 2625 synthetic variants of pistol ribozymes, and screened for active variants directly in mammalian cells, greatly expanding the ribozyme toolbox for biological applications
Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells
Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the first step in neurogenesis. We further assessed the effect of TBT on neural differentiation and found that it reduced the expression of several neural differentiation marker genes, which were also downregulated by Mfn1 knockdown in iPSCs. Taken together, these results indicate that TBT induces developmental neurotoxicity via Mfn1-mediated mitochondrial dysfunction in iPSCs
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