Rhythmic interaction between Period1 mRNA and HnRNP Q leads to circadian time-dependent translation

The mouse PERIOD1 (mPER1) protein, along with other clock proteins, plays a crucial role in the maintenance of circadian rhythms. mPER1 also provides an important link between the circadian system and the cell cycle system. Here we show that the circadian expression of mPER1 is regulated by rhythmic translational control of mPer1 mRNA together with transcriptional modulation. This time-dependent translation was controlled by an internal ribosomal entry site (IRES) element in the 5' untranslated region (5'-UTR) of mPer1 mRNA along with the trans-acting factor mouse heterogeneous nuclear ribonucleoprotein Q (mhnRNP Q). Knockdown of mhnRNP Q caused a decrease in mPER1 levels and a slight delay in mPER1 expression without changing mRNA levels. The rate of IRES-mediated translation exhibits phase-dependent characteristics through rhythmic interactions between mPer1 mRNA and mhnRNP Q. Here, we demonstrate 5'-UTR-mediated rhythmic mPer1 translation and provide evidence for posttranscriptional regulation of the circadian rhythmicity of core clock genes.X112932sciescopu

Water-Repellent TiO₂-Organic Dye-Based Air Filters for Efficient Visible-Light-Activated Photochemical Inactivation against Bioaerosols

Recently, bioaerosols, including the 2019 novel coronavirus, pose a serious threat to global public health. Herein, we introduce a visible-light-activated (VLA) antimicrobial air filter functionalized with titanium dioxide (TiO2)–crystal violet (CV) nanocomposites facilitating abandoned visible light from sunlight or indoor lights. The TiO2–CV based VLA antimicrobial air filters exhibit a potent inactivation rate of ∼99.98% and filtration efficiency of ∼99.9% against various bioaerosols. Under visible-light, the CV is involved in overall inactivation by inducing reactive oxygen species production both directly (CV itself) and indirectly (in combination with TiO2). Moreover, the susceptibility of the CV to humidity was significantly improved by forming a hydrophobic molecular layer on the TiO2 surface, highlighting its potential applicability in real environments such as exhaled or humid air. We believe this work can open a new avenue for designing and realizing practical antimicrobial technology using ubiquitous visible-light energy against the threat of infectious bioaerosols

Detecting Variability in Massive Astronomical Time-Series Data I: application of an infinite Gaussian mixture model

We present a new framework to detect various types of variable objects within massive astronomical time-series data. Assuming that the dominant population of objects is non-variable, we find outliers from this population by using a non-parametric Bayesian clustering algorithm based on an infinite GaussianMixtureModel (GMM) and the Dirichlet Process. The algorithm extracts information from a given dataset, which is described by six variability indices. The GMM uses those variability indices to recover clusters that are described by six-dimensional multivariate Gaussian distributions, allowing our approach to consider the sampling pattern of time-series data, systematic biases, the number of data points for each light curve, and photometric quality. Using the Northern Sky Variability Survey data, we test our approach and prove that the infinite GMM is useful at detecting variable objects, while providing statistical inference estimation that suppresses false detection. The proposed approach will be effective in the exploration of future surveys such as GAIA, Pan-Starrs, and LSST, which will produce massive time-series data.Comment: accepted for publication in MNRA

Studies of salivary pepsin in patients with gastro‐oesophageal reflux disease

Background Gastro‐oesophageal reflux disease (GERD) is difficult to diagnose without invasive testing. Peptest (RD Biomed, Hull, UK) is a recently marketed diagnostic tool which aims to quantify salivary pepsin as a marker of reflux, providing a rapid alternative to invasive procedures. Aim To evaluate optimal timing for sampling, and to evaluate the accuracy of Peptest against an independent measure. Methods Thirty diagnosed GERD patients (12 female, mean age 49 [range 20‐72]) and 20 asymptomatic subjects (14 female, mean age 56 [range 21‐56]) were subject to diurnal saliva sampling, with additional samples for 60 minutes following self‐reported reflux symptoms and triggering of a proximal reflux alarm. Saliva samples were split and were analysed by both Peptest and ELISA with operators for each blinded to sample identity. Results Salivary pepsin was detectable in most patients and most volunteers. Peptest scores were significantly lower for patients than controls (P < 0.005). ELISA scores showed no difference between patients and controls. There was no effect of diurnal sampling time (P = 0.75) or time after symptoms (P = 0.76) on Peptest readout. There was no correlation between Peptest and Pepsin ELISA (P = 0.55); Bland‐Altman analysis suggested no agreement between the tests (P = 0.414). Receiver‐operator curve suggests that neither Peptest (P = 0.3328) nor pepsin (P = 0.4476) is useful for predicting GERD. Conclusion Salivary pepsin is not a reliable tool for the diagnosis of GERD

Bio-anthropological Studies on Human Skeletons from the 6th Century Tomb of Ancient Silla Kingdom in South Korea

In November and December 2013, unidentified human skeletal remains buried in a mokgwakmyo (a traditional wooden coffin) were unearthed while conducting an archaeological investigation near Gyeongju, which was the capital of the Silla Kingdom (57 BCE– 660 CE) of ancient Korea. The human skeletal remains were preserved in relatively intact condition. In an attempt to obtain biological information on the skeleton, physical anthropological, mitochondrial DNA, stable isotope and craniofacial analyses were carried out. The results indicated that the individual was a female from the Silla period, of 155 ± 5 cm height, who died in her late thirties. The maternal lineage belonged to the haplogroup F1b1a, typical for East Asia, and the diet had been more C3- (wheat, rice and potatoes) than C4-based (maize, millet and other tropical grains). Finally, the face of the individual was reconstructed utilizing the skull (restored from osseous fragments) and three-dimensional computerized modelling system. This study, applying multi-dimensional approaches within an overall bio-anthropological analysis, was the first attempt to collect holistic biological information on human skeletal remains dating to the Silla Kingdom period of ancient Korea

Simultaneous or Sequential Orthogonal Gradient Formation in a 3D Cell Culture Microfluidic Platform

Biochemical gradients are ubiquitous in biology. At the tissue level, they dictate differentiation patterning or cell migration. Recapitulating in vitro the complexity of such concentration profiles with great spatial and dynamic control is crucial in order to understand the underlying mechanisms of biological phenomena. Here, a microfluidic design capable of generating diffusion-driven, simultaneous or sequential, orthogonal linear concentration gradients in a 3D cell-embedded scaffold is described. Formation and stability of the orthogonal gradients are demonstrated by computational and fluorescent dextran-based characterizations. Then, system utility is explored in two biological systems. First, stem cells are subjected to orthogonal gradients of morphogens in order to mimic the localized differentiation of motor neurons in the neural tube. Similarly to in vivo, motor neurons preferentially differentiate in regions of high concentration of retinoic acid and smoothened agonist (acting as sonic hedgehog), in a concentration-dependent fashion. Then, a rotating gradient is applied to HT1080 cancer cells and the change in migration direction is investigated as the cells adapt to a new chemical environment. The response time of ≈4 h is reported. These two examples demonstrate the versatility of this new design that can also prove useful in many applications including tissue engineering and drug screening.National Science Foundation. Science and Technology Center for Emergent Behaviors of Integrated Cellular Systems (Grant No. CBET-0939511)National Institutes of Health (U.S.) (NIH NRSA/UNCF Merck

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

Recruitment Potential of a Green Alga Ulva flexuosa Wulfen Dark Preserved Zoospore and Its Development

The recruitment potential and the ability of Ulva flexuosa Wulfen zoospores to survive darkness were tested under different conditions in the present study. The dark preserved zoospore was cultured under a two-factor experimental design to test the effect of salinity and nitrate, effect of salinity and phosphate, effect of light and salinity, and effect of light and phosphate. The recruitment (germination and growth) of zoospores was significantly affected by light and salinity. The nitrate concentration of 20 µmol.l−1 was found to initiate the process of germination and its subsequent growth and, its effect appeared greatest under 25 psu condition. While nitrate enhances the growth of biomass more than phosphate, both show a positive interactive effect on biomass increase when crossed with salinity. The combined effect of 25 psu salinity and 8 µmol.l−1 phosphate exhibited higher biomass growth. There was a significant effect of light and salinity on the biomass of zoospore, though there was no significant interaction between the two factors. There was an increase in biomass of growing zoospores to increase in light intensity and 80 µmol.m−2.s−1 of light intensity was considered optimal. Similarly, high light intensity condition favored higher biomass growth and there was significant interaction between light (80 µmol. m−2. s−1) and phosphate (4 µmol. l−1) in high salinity (35 psu) condition. The result of this study showed that dark preserved zoospores of U. flexuosa have the potential for recruitment and it gives us an understanding how different factors play a role in the process of recruitment

Smyd3 Is Required for the Development of Cardiac and Skeletal Muscle in Zebrafish

Modifications of histone tails are involved in the regulation of a wide range of biological processes including cell cycle, cell survival, cell division, and cell differentiation. Among the modifications, histone methylation plays a critical role in cardiac and skeletal muscle differentiation. In our earlier studies, we found that SMYD3 has methyltransferase activity to histone H3 lysine 4, and that its up-regulation is involved in the tumorigenesis of human colon, liver, and breast. To clarify the role of Smyd3 in development, we have studied its expression patterns in zebrafish embryos and the effect of its suppression on development using Smyd3-specific antisense morpholino-oligonucleotides. We here show that transcripts of smyd3 were expressed in zebrafish embryos at all developmental stages examined and that knockdown of smyd3 in embryos resulted in pericardial edema and defects in the trunk structure. In addition, these phenotypes were associated with abnormal expression of three heart-chamber markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic regulatory factors including myod and myog. These data suggest that Smyd3 plays an important role in the development of heart and skeletal muscle