Neuroprotective effect of dexmedetomidine on autophagy in mice administered intracerebroventricular injections of Aβ25–35

Alzheimer’s disease (AD), one of the most prevalent neurodegenerative diseases is associated with pathological autophagy-lysosomal pathway dysfunction. Dexmedetomidine (Dex) has been suggested as an adjuvant to general anesthesia with advantages in reducing the incidence of postoperative cognitive dysfunction in Dex-treated patients with AD and older individuals. Several studies reported that Dex improved memory; however, evidence on the effects of Dex on neuronal autophagy dysfunction in the AD model is lacking. We hypothesized that Dex administration would have neuroprotective effects by improving pathological autophagy dysfunction in mice that received an intracerebroventricular (i.c.v.) injection of amyloid β-protein fragment 25–35 (Aβ25–35) and in an autophagy-deficient cellular model. In the Y-maze test, Dex reversed the decreased activity of Aβ25–35 mice. Additionally, it restored the levels of two memory-related proteins, phosphorylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII) and postsynaptic density-95 (PSD-95) in Aβ25–35 mice and organotypic hippocampal slice culture (OHSC) with Aβ25–35. Dex administration also resulted in decreased expression of the autophagy-related microtubule-associated proteins light chain 3-II (LC3-II), p62, lysosome-associated membrane protein2 (LAMP2), and cathepsin D in Aβ25–35 mice and OHSC with Aβ25–35. Increased numbers of co-localized puncta of LC3-LAMP2 or LC3-cathepsin D, along with dissociated LC3-p62 immunoreactivity following Dex treatment, were observed. These findings were consistent with the results of western blots and the transformation of double-membrane autophagosomes into single-membraned autolysosomes in ultrastructures. It was evident that Dex treatment alleviated impaired autolysosome formation in Aβ mice. Our study demonstrated the improvement of memory impairment caused by Dex and its neuroprotective mechanism by investigating the role of the autophagy-lysosomal pathway in a murine Aβ25–35 model. These findings suggest that Dex could be used as a potential neuroprotective adjuvant in general anesthesia to prevent cognitive decline

Kalman Filter-based Data Recovery in Wireless Smart Sensor Network for Infrastructure Monitoring

Extensive research effort has been made during the last decade to utilize wireless smart sensors for evaluating and monitoring structural integrity of civil engineering structures. The wireless smart sensor commonly has sensing and embedded computation capabilities as well as wireless communication that provide strong potential to overcome shortcomings of traditional wired sensor systems such as high equipment and installation cost. However, sensor malfunctioning particularly in case of long-term monitoring and unreliable wireless communication in harsh environment are the critical issues that should be properly tackled for a wider adoption of wireless smart sensors in practice. This study presents a wireless smart sensor network(WSSN) that can estimate unmeasured responses for the purpose of data recovery at unresponsive sensor nodes. A software program that runs on WSSN is developed to estimate the unmeasured responses from the measured using the Kalman filter. The performance of the developed network software is experimentally verified by estimating unmeasured acceleration responses using a simply-supported beam.clos

Inflammatory Signals Induce AT2 Cell-Derived Damage-Associated Transient Progenitors that Mediate Alveolar Regeneration.

Tissue regeneration is a multi-step process mediated by diverse cellular hierarchies and states that are also implicated in tissue dysfunction and pathogenesis. Here we leveraged single-cell RNA sequencing in combination with in vivo lineage tracing and organoid models to finely map the trajectories of alveolar-lineage cells during injury repair and lung regeneration. We identified a distinct AT2-lineage population, damage-associated transient progenitors (DATPs), that arises during alveolar regeneration. We found that interstitial macrophage-derived IL-1β primes a subset of AT2 cells expressing Il1r1 for conversion into DATPs via a HIF1α-mediated glycolysis pathway, which is required for mature AT1 cell differentiation. Importantly, chronic inflammation mediated by IL-1β prevents AT1 differentiation, leading to aberrant accumulation of DATPs and impaired alveolar regeneration. Together, this stepwise mapping to cell fate transitions shows how an inflammatory niche controls alveolar regeneration by controlling stem cell fate and behavior.We would like to thank Emma Rawlins (University of Cambridge, UK) for valuable scientific discussions and sharing the mouse lines; We would like to thank Randall Johnson (University of Cambridge, UK) for sharing Hif1aflox/flox mouse line; Nisha Narayan and Brian Huntly for sharing materials and discussion on glycolysis experiments; Irina Pshenichnaya (Histology), Maike Paramor (NGS library), Peter Humphreys (Imaging), Andy Riddell (Flow cytometry), Simon McCallum (Flow cytometry, Cambridge NIHR BRC Cell Phenotyping Hub), Katarzyna Kania (single cell sequencing at Cancer Research UK), and Cambridge Stem Cell Institute core facilities for technical assistance; Papworth Hospital Research Tissue Bank for providing tissue samples from IPF and lung adenocarcinoma (T02233); Kelly Evans for sharing histology samples of human lung tissue samples; Seungmin Han and Woochang Hwang for discussion on the scRNA-seq analysis; Life Science Editors for editorial assistance; All Lee Lab members for helpful discussion. This work was supported by Wellcome and the Royal Society (107633/Z/15/Z) and European Research Council Starting Grant (679411). J.C. was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2017R1A6A3A03005399)

Contrast Sensitivity Function of Sound Eye after Occlusion Therapy in the Amblyopic Children

To verify the changes of mesopic and photopic contrast sensitivity function of sound eye whose visual acuity was kept the same after occlusion therapy in the amblyopic children. Fourteen sound eyes of amblyopic children (mean; 7.67 years; S.D., 1.50 years) who kept their visual acuity the same after the occlusion therapy were tested. The children had 6 hours of part-time patch therapy for 3 months prior to this examination. Among 14 amblyopic children, 8 were anisometric and 6 were strabismic amblyopes. Using the visual capacity analyzer which measures the minimal contrast level at from low to high spatial frequencies, the contrast sensitivity of sound eye was measured, under both photopic and mesopic condition, before and after 3 months of occlusion therapy. Comparing the contrast sensitivity of sound eye after the occlusion therapy to that before the occlusion, there was no statistical difference in photopic condition. When it comes to mesopic condition, the contrast sensitivity decreased at the intermediate spatial frequency level (3-13 c.p.d, p=0.028) after the occlusion therapy. The occlusion caused statistically significant decrease in mesopic contrast sensitivity, when the visual acuity was not changed after the occlusion therapy. It may indicate that mesopic contrast sensitivity can be considered as a useful tool for early detection of hidden occlusion amblyopia

Discrimination of Kawasaki disease with concomitant adenoviral detection differentiating from isolated adenoviral infection

PurposeHuman adenovirus infection mimics Kawasaki disease (KD) but can be detected in KD patients. The aim of this study was to determine the clinical differences between KD with adenovirus infection and only adenoviral infection and to identify biomarkers for prediction of adenovirus-positive KD from isolated adenoviral infection.MethodsA total of 147 patients with isolated adenovirus were identified by quantitative polymerase chain reaction. In addition, 11 patients having KD with adenovirus, who were treated with intravenous immunoglobulin therapy during the acute phase of KD were also evaluated.ResultsCompared with the adenoviral infection group, the KD with adenovirus group was significantly associated with frequent lip and tongue changes, skin rash and changes in the extremities. In the laboratory parameters, higher C-reactive protein (CRP) level and presence of hypoalbuminemia and sterile pyuria were significantly associated with the KD group. In the multivariate analysis, lip and tongue changes (odds ratio [OR], 1.416; 95% confidence interval [CI], 1.151–1.741; P=0.001), high CRP level (OR, 1.039; 95% CI 1.743–1.454; P= 0.021) and sterile pyuria (OR 1.052; 95% CI 0.861–1.286; P=0.041) were the significant predictive factors of KD. In addition, the cutoff CRP level related to KD with adenoviral detection was 56 mg/L, with a sensitivity of 81.8% and a specificity of 75.9%.ConclusionLip and tongue changes, higher serum CRP level and sterile pyuria were significantly correlated with adenovirus-positive KD

Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice

Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits. Model organisms play a crucial role in the identification of such gene-by-environment interactions, as a result of the unique ability to observe genetically similar individuals across multiple distinct environments. Many model organism studies examine the same traits but under varying environmental conditions. For example, knock-out or diet-controlled studies are often used to examine cholesterol in mice. These studies, when examined in aggregate, provide an opportunity to identify genomic loci exhibiting environmentally-dependent effects. However, the straightforward application of traditional methodologies to aggregate separate studies suffers from several problems. First, environmental conditions are often variable and do not fit the standard univariate model for interactions. Additionally, applying a multivariate model results in increased degrees of freedom and low statistical power. In this paper, we jointly analyze multiple studies with varying environmental conditions using a meta-analytic approach based on a random effects model to identify loci involved in gene-by-environment interactions. Our approach is motivated by the observation that methods for discovering gene-by-environment interactions are closely related to random effects models for meta-analysis. We show that interactions can be interpreted as heterogeneity and can be detected without utilizing the traditional uni- or multi-variate approaches for discovery of gene-by-environment interactions. We apply our new method to combine 17 mouse studies containing in aggregate 4,965 distinct animals. We identify 26 significant loci involved in High-density lipoprotein (HDL) cholesterol, many of which are consistent with previous findings. Several of these loci show significant evidence of involvement in gene-by-environment interactions. An additional advantage of our meta-analysis approach is that our combined study has significantly higher power and improved resolution compared to any single study thus explaining the large number of loci discovered in the combined study

Complete genome sequence of Mycobacterium tuberculosis K from a Korean high school outbreak, belonging to the Beijing family

Mycobacterium tuberculosis K, a member of the Beijing family, was first identified in 1999 as the most prevalent genotype in South Korea among clinical isolates of M. tuberculosis from high school outbreaks. M. tuberculosis K is an aerobic, non-motile, Gram-positive, and non-spore-forming rod-shaped bacillus. A transmission electron microscopy analysis displayed an abundance of lipid bodies in the cytosol. The genome of the M. tuberculosis K strain was sequenced using two independent sequencing methods (Sanger and Illumina). Here, we present the genomic features of the 4,385,518-bp-long complete genome sequence of M. tuberculosis K (one chromosome, no plasmid, and 65.59 % G + C content) and its annotation, which consists of 4194 genes (3447 genes with predicted functions), 48 RNA genes (3 rRNA and 45 tRNA) and 261 genes with peptide signals.

Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo

Nutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. We examined the specific inhibitory effects of amino acid deprivation on the metastatic phenotypes of the human triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and Hs 578T, as well as the orthotopic 4T1 mouse TNBC tumor model. Among the 10 essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase, as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 and MMP-9, two major markers of metastasis, while increasing the mRNA expression of tissue inhibitor of metalloproteinase 1 in MDA-MB-231 cells. Furthermore, methionine restriction downregulated the metastasis-related factor urokinase plasminogen activatior and upregulated plasminogen activator inhibitor 1 mRNA expression. Animals on the methionine-deprived diet showed lower lung metastasis rates compared to mice on the control diet. Taken together, these results suggest that methionine restriction could provide a potential nutritional strategy for more effective cancer therapy

Molecular Identification of Taenia Tapeworms by Cox1 Gene in Koh Kong, Cambodia

We collected fecal samples from 21 individuals infected with Taenia tapeworms in Koh Kong Province, Cambodia, and performed nucleotide sequencing of the cox1 gene and multiplex PCR on the eggs for DNA differential diagnosis of human Taenia tapeworms. Genomic DNA was extracted from the eggs of a minimum number of 10 isolated from fecal samples. Using oligonucleotide primers Ta7126F, Ts7313F, Tso7466F, and Rev7915, the multiplex PCR assay proved useful for differentially diagnosing Taenia solium, Taenia saginata, and Taenia asiatica based on 706, 629, and 474 bp bands, respectively. All of the Taenia specimens from Kho Kong, Cambodia, were identified as either T. saginata (n=19) or T. solium (n=2) by cox1 sequencing and multiplex PCR