An Entosis-Like Process Induces Mitotic Disruption in Pals1 Microcephaly Pathogenesis

Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing gene Pals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely abrogates CIC structures and restores the normal length of mitosis. Moreover, genetic elimination of Trp53 produces a remarkable rescue of cortical size along with substantial reductions of CIC structures and cell death. These results provide a novel pathogenic mechanism by which microcephaly is produced through entotic cell cannibalism

Dual function of Yap in the regulation of lens progenitor cells and cellular polarity

AbstractHippo-Yap signaling has been implicated in organ size determination via its regulation of cell proliferation, growth and apoptosis (Pan, 2007). The vertebrate lens comprises only two major cell types, lens progenitors and differentiated fiber cells, thereby providing a relatively simple system for studying size-controlling mechanisms. In order to investigate the role of Hippo-Yap signaling in lens size regulation, we conditionally ablated Yap in the developing mouse lens. Lens progenitor-specific deletion of Yap led to near obliteration of the lens primarily due to hypocellularity in the lens epithelium (LE) and accompanying lens fiber (LF) defects. A significantly reduced LE progenitor pool resulted mainly from failed self-renewal and increased apoptosis. Additionally, Yap-deficient lens progenitor cells precociously exited the cell cycle and expressed the LF marker, β-Crystallin. The mutant progenitor cells also exhibited multiple cellular and subcellular alterations including cell and nuclear shape change, organellar polarity disruption, and disorganized apical polarity complex and junction proteins such as Crumbs, Pals1, Par3 and ZO-1. Yap-deficient LF cells failed to anchor to the overlying LE layer, impairing their normal elongation and packaging. Furthermore, our localization study results suggest that, in the developing LE, Yap participates in the cell context-dependent transition from the proliferative to differentiation-competent state by integrating cell density information. Taken together, our results shed new light on Yap's indispensable and novel organizing role in mammalian organ size control by coordinating multiple events including cell proliferation, differentiation, and polarity

Vaccine effectiveness and the epidemiological characteristics of a COVID-19 outbreak in a tertiary hospital in Republic of Korea

Objectives Healthcare facilities are high-risk sites for infection. This study analyzed the epidemiological characteristics of a coronavirus disease 2019 (COVID-19) outbreak in a tertiary hospital after COVID-19 vaccination had been introduced in Republic of Korea. Vaccine effectiveness (VE) and shared anti-infection strategies are also assessed. Methods The risk levels for 4,074 contacts were evaluated. The epidemiological characteristics of confirmed cases were evaluated using the chi-square test. The “1 minus relative risk” method was used to determine VE in preventing infection, progression to severe disease, and death. In the largest affected area (the 8th floor), a separate relative risk analysis was conducted. A multivariate logistic regression analysis (with 95% confidence interval [CIs]) was used to identify transmission risk factors with a significance level <10% via the backward elimination method. Results In total, 181 cases of COVID-19 were confirmed, with an attack rate of 4.4%. Of those cases, 12.7% progressed to severe disease, and 8.3% died. In the cohort isolation area on the 8th floor, where 79.0% of the confirmed cases occurred, the adjusted odds ratio was 6.55 (95% CI, 2.99–14.33) and 2.19 (95% CI, 1.24–3.88) for caregivers and the unvaccinated group, respectively. VE analysis revealed that 85.8% of the cases that progressed to severe disease and 78.6% of the deaths could be prevented by administering a second vaccine. Conclusion Caregiver training for infection prevention and control is necessary to reduce infection risk. Vaccination is an important intervention to reduce the risk of progression to severe disease and death

High-throughput intracellular delivery of proteins and plasmids

Intracellular delivery of macromolecules is crucial for the success of many research and clinical applications. Several conventional intracellular delivery methods have been used for many years but are still inadequate for several applications because of the issues associated with toxicity, low-throughput, and/or difficulty to target certain cell types. In this study, we developed and evaluated new high-throughput intracellular delivery methods for the efficient delivery of macromolecules while maintaining high cell viability. First, we studied the feasibility of using an array of nanoneedles, with sharp tip diameters in the range of tens of nanometers, to physically make transient holes in cell membranes for intracellular delivery. Puncture loading and centrifuge loading methods were developed and assessed for the effect of various experimental parameters on cell viability and delivery efficiency of fluorescent molecules. In both methods, high-throughput intracellular delivery was feasible by creating transient holes in cell membranes with the sharp tips of the nanoneedles. The second physical intracellular delivery method we studied was a novel microfluidic device that created transient holes in the cell membrane by mechanical deformation and shear stress to the cell. We observed efficient delivery of fluorescent molecules and studied the effect of device design and flow pressure on the delivery efficiency compared to data in the literature. We accounted for cell loss and clogging in the microfluidic devices and determined the true loss of cell viability associated with this method. Lastly, we investigated the possibility of intracellular delivery using nanoparticles on a leukemia cell line. Among number of materials for nanoparticles tested, mesoporous silica/poly-L-lysine nanoparticles were selected for further intracellular delivery study based on cell viability and intracellular delivery capability. We demonstrated the co-delivery of protein and plasmid by encapsulating into and coating onto the surface of the nanoparticles, respectively, which would be advantageous for certain therapeutic strategies. In summary, this work introduced two new intracellular delivery methods involving nanoneedles and novel nanoparticles, and provided an early, independent assessment of microfluidic delivery, showing the strengths and weaknesses of each method. These methods can be further optimized for a number of laboratory and clinical applications with continued research.Ph.D

Sulfur-Utilizing Autotrophic Denitrification Process for the Treatment of Nitrate-Rich Water

As the increasing concentration of nitrogen contamination in the water is becoming a problem in many places, this project studied the method for the treatment of nitrate-rich water using the autotrophic denitrification process. The effects of environmental and running conditions were observed using the batch and continuous reactors. The autotrophic denitrification process was able to treat nitrate or nitrite-rich water, but probably cannot be used for the treatment of drinking water. The result showed that the process works well for acidic pH, temperature higher than 15 176C and at HRT above 3

Detect of Novel Alternative Form at Development Stages in Brain

this paper, we use the development information of ESTs to detect novel alternative form in Brain. We explain the expression pattern of gene for each development stage. Moreover, we expect that specific splice variants are associated with mouse disease of brain specifi

Reduce, Reuse, and Replace: A Study on Solutions to Plastic Wastes

This project aimed to examine the quantities of plastic wastes discarded and the fate of various plastics in the environment. Our Interactive Qualifying Project was concerned with researching the possible alternatives to plastics, mainly biodegradable plastics that have been claimed to biodegrade and help environment. Moreover, it was also required to evaluate the best methods to deal with our plastic wastes that are environmentally, economically, and energy-wise viable

Image Dehazing and Enhancement Using Principal Component Analysis and Modified Haze Features

This paper presents a computationally efficient haze removal and image enhancement methods. The major contribution of the proposed research is two-fold: (i) an accurate atmospheric light estimation using principal component analysis, and (ii) learning-based transmission estimation. To reduce the computational cost, we impose a constraint on the candidate pixels to estimate the haze components in the sub-image. In addition, the proposed method extracts modified haze-relevant features to estimate an accurate transmission using random forest. Experimental results show that the proposed method can provide high-quality results with a significantly reduced computational load compared with existing methods. In addition, we demonstrate that the proposed method can significantly enhance the contrast of low-light images according to the assumption on the visual similarity between the inverted low-light and haze images

Low-light image restoration using bright channel prior-based variational Retinex model

Abstract This paper presents a low-light image restoration method based on the variational Retinex model using the bright channel prior (BCP) and total-variation minimization. The proposed method first estimates the bright channel to control the amount of brightness enhancement. Next, the variational Retinex-based energy function is iteratively minimized to estimate the improved illumination and reflectance using the BCP. Contrast of the estimated illumination is enhanced using the gamma correction and histogram equalization to reduce a color distortion and noise amplification. Experimental results show that the proposed method can provide the better restored result than the existing methods without unnatural artifacts such as noise amplification and halo effects near edges